Madeline Shea, PhD

Portrait
Professor of Biochemistry
Professor of Molecular Physiology and Biophysics

Contact Information

Primary Office
4-450 BSB
Iowa City, IA 52242
319-335-7885

Education

PhD, T.C. Jenkins Dept. of Biophysics, The Johns Hopkins University
BS, Chemistry, California Institute of Technology
Fellow, Dept. of Biology, The Johns Hopkins University

Education/Training Program Affiliations

Department of Biochemistry PhD, Interdisciplinary Graduate Program in Translational Biomedicine, Medical Scientist Training Program

Center, Program and Institute Affiliations

Center for Biocatalysis and Bioprocessing

Research Summary

This laboratory probes the linkage between cooperative ligand binding, conformational change and enzyme activation by calmodulin, a regulatory calcium- binding protein. Calmodulin is the primary eukaryotic intracellular calcium receptor and serves as a second messenger to regulate cellular responses to transient calcium fluxes. It is clinically relevant for human physiology and is also found in plants and fungi. Cooperative binding of calcium ions to calmodulin causes large conformational changes; these changes control the sites and extent of calmodulin activation of important cellular enzymes and structural proteins. In order to determine the states that are functionally significant in this complex network of interactions, it is necessary to develop and apply new methods to directly determine energetic and structural properties of calcium binding. Quantitative proteolytic footprinting and applications of multi-dimensional heteronuclear NMR are capable of monitoring individual residues or bonds during a titration representative of a cellular influx of calcium. These studies have shown that the two domains of calmodulin interact in different ways as calcium fills the four sites of the protein. X-ray crystallography is used to determine how the domains interact with peptides that represent CaM-binding motifs in target proteins. Calcium-dependent structural rearrangements of calmodulin also are monitored by changes in the fluorescence, circular dichroism and hydrodynamic properties. These combined approaches are aimed at elucidating molecular mechanisms of cooperativity in calmodulin by determining the differences in intrinsic binding affinity at the four calcium-binding sites of calmodulin and the extent and nature of inter- and intra-domain cooperativity. To dissect these interactions, we are studying the isolated domains of calmodulin and many mutants shown to have phenotypic effects on complexes of calmodulin with its target enzymes. Computational molecular modeling is used to visualize and calculate properties of these proteins and serves as a complement to the experimental studies of ligand- linked conformational change. The goal is to combine energetic and structural data to formulate models that will explain how synchronized changes in calcium levels modulate many diverse physiological processes.

Publications

Marsden, A., Derry, S., Schneider, I., Scott, C., Westfall, T., Branstrom, L., Shea, M. A., Dawson, D. V. & Slusarski, D. C. (2018). The Nkd EF-Hand Domain Modulates Divergent Wnt Signaling Outputs in Zebrafish Developmental Biology.

Mahling, R., Kilpatrick, A. M. & Shea, M. A. (2017). Backbone resonance assignments of complexes of human voltage-dependent sodium channel NaV1.2 IQ motif peptide bound to apo calmodulin and to the C-domain fragment of apo calmodulin. Biomolecular NMR assignments. PMID: 28823028.

Fowler, C. A., Núñez Hernandez, M. F., O'Donnell, S. E., Yu, L. & Shea, M. A. (2017). Backbone and side-chain resonance assignments of (Ca2+)4-calmodulin bound to beta calcineurin A CaMBD peptide. Biomolecular NMR assignments. PMID: 28815458.

Hovey, L., Fowler, C. A., Mahling, R., Lin, Z., Miller, M. S., Marx, D. C., Yoder, J. B., Kim, E. H., Tefft, K. M., Waite, B. C., Feldkamp, M. D., Yu, L. & Shea, M. A. (2017). Calcium triggers reversal of calmodulin on nested anti-parallel sites in the IQ motif of the neuronal voltage-dependent sodium channel NaV1.2. Biophysical chemistry, 224, 1-19. PMID: 28343066.

(2017). Crystal Structure of Ca2+/Calmodulin bound to NMDA Receptor NR1C1 peptide (2HQW). rcsb.org.

(2017). Backbone chemical shift assignments of Apo Human Calmodulin C-domain bound to Human Na1.2 IQ motif peptide (Mahling et al) 27094. www.bmrb.wisc.edu.

(2017). Backbone chemical shift assignments of Apo Human Calmodulin (full-length) bound to Human Na1.2 IQ motif peptide (mahling et al) 27095.

Weaver, L. D., Uribe, B. R., Nunez-Hernandez, M., Rendleman, M. C., Klein, S. A., O'Donnell, S. E. & Shea, M. A. (2016). CaN Regulation of Calcineurin by Calcium-Binding Cousins. (Vols. 108). pp. 108a. Biophysical Journal.

Mahling, R., Fowler, C. A., Hovey, L., Yu, L., Gakhar, L., Lin, Z., Pandey, N., Martins, T. J. & Shea, M. A. (2016). Structural Differences in Calmodulin Bound to Voltage-gated sodium channel IQ motifs. (Vols. 110). pp. 109a. Biophysical Journal.

Isbell, H. M., Kilpatrick, A. M., Lin, Z. & Shea, M. A. (2016). Calmodulin recognition of voltage gated sodium channels Nav1.1,Nav1.4, and Nav1.7. (Vols. 112). Biophysical Journal.

Mahling, R., Kilpatrick, A. M., Isbell, H. M., Lin, Z. & Shea, M. A. (2016). intermediate states and structural ensembles of calmodulin bound to the Nav1.2 IQ motif. (Vols. 112). Biophysical Journal.

Feldkamp, M. D., Gakhar, L., Pandey, N. & Shea, M. A. (2015). Opposing orientations of the anti-psychotic drug trifluoperazine selected by alternate conformations of M144 in calmodulin. Proteins, 83(5), 989-96. PMID: 25694384.

Hovey, L., Andersen, C., Marx, D. & Shea, M. A. (2015). Recruitment of Calmodulin to the Tail of the Voltage gated sodium channel Nav1.2. (Vols. 108). pp. 577a. Biophysical Journal.

Newman, R. A., Sorensen, B. R., Kilpatrick, A. M. & Shea, M. A. (2014). Calcium-dependent energetics of calmodulin domain interactions with regulatory regions of the Ryanodine Receptor Type 1 (RyR1). Biophys Chem, 193-194, 35-49. PMID: 25145833.

Wang, X., Boyken, S. E., Hu, J., Xu, X., Rimer, R. P., Shea, M. A., Shaw, A. S., Andreotti, A. H. & Huang, Y. H. (2014). Calmodulin and PI(3,4,5)P3 cooperatively bind to the Itk pleckstrin homology domain to promote efficient calcium signaling and IL-17A production. Sci. Signal, 7, 337. PMID: 25097034.

Hovey, L., Miller, M. S., Marx, D. C., Tefft, K. M., Kim, E., Yoder, J. B. & Shea, M. A. (2014). Determinants of Preferential Binding of Apo Calmodulin to the IQ motif of Neuronal Sodium Channel Nav1.2. (Vols. 106). pp. 679a. Biophysical Journal.

Marx, D. C., Miller, M. S., Hovey, L., Tefft, K. M., Yoder, J. B., Kim, E., Martin, S. C., Feldkamp, M. D. & Shea, M. A. (2014). Specificity of Calmodulin Recognition of Human Voltage Gated Sodium Channels. Biophysical Journal.

Miller, M. S., Fowler, C. A., Feldkamp, M. D., Yu, L. & Shea, M. A. (2014). Calcium-Mediated Reversal of CaM on the NaV 1.2 IQ Motif: Nested Anti-Parallel Sites. (Vols. 106). pp. 48a. Biophysical Journal.

Shea, M. A., Klein, S. A., O'Donnell, S. E., Waite, B. C. & Yoder, J. B. (2014). Calcium-mediated regulation of Calcineurin by a Dynamic Duo of EF-Hand proteins. (Vols. 106). pp. 679a. Biophysical Journal.

Kilpatrick, A. M., Marwitz, A., Tefft, K., Weaver, L. & Shea, M. A. (2014). Thermodynamic analysis of calmodulin recognition of the ion channel ryanodine receptor. (Vols. 106). pp. 527a. Biophysical Journal.

Shea, M. A., Miller, M. S., Yoder, J. B., Fowler, C. A. & Feldkamp, M. D. (2013). Calcium-Mediated Tailspin of Calmodulin on the IQ Motif of the Neuronal Voltage Dependent Sodium Channel Nav1.2. (Vols. 104). pp. 14a. Biophysical Journal.

Dagan, M. C., Elaine, K. H., Miller, M., Yoder, J., Martin, S., Tarleton, D. `., Waite, B. C., Feldkamp, M. D. & Shae, M. A. (2013). Two classes of calmodulin binding to IQ motifs of voltage gated sodium channels. (Vols. 104). pp. 100a. Biophysical Journal.

Klein, S., Waite, B., O'Donnell, S., Yoder, J. B. & Shea, M. A. (2013). Regulation of Calcineurin by Domain specific interactions of calmodulin. (Vols. 104). pp. 100a. Biophysical Journal.

Shea, M. A., Correia, J. J. & Brenowitz, M. D. (2011). Introduction: twenty five years of the Gibbs Conference on Biothermodynamics. Biophysical Chemistry, 159(1), 1-5. PMID: 21840113.

Evans, T. I., Hell, J. W. & Shea, M. A. (2011). Thermodynamic linkage between calmodulin domains binding calcium and contiguous sites in the C-terminal tail of Ca(V)1.2. Biophysical Chemistry, 159(1), 172-87. PMID: 21757287.

Feldkamp, M. D., Yu, L. & Shea, M. A. (2011). Structural and energetic determinants of apo calmodulin binding to the IQ motif of the Na(V)1.2 voltage-dependent sodium channel. Structure (London, England: 1993), 19(5), 733-47. PMID: 21439835.

O'Donnell, S. E., Yu, L., Fowler, C. A. & Shea, M. A. (2011). Recognition of ß-calcineurin by the domains of calmodulin: thermodynamic and structural evidence for distinct roles. Proteins, 79(3), 765-86. PMID: 21287611.

Feldkamp, M. D., O'Donnell, S. E., Yu, L. & Shea, M. A. (2010). Allosteric effects of the antipsychotic drug trifluoperazine on the energetics of calcium binding by calmodulin. Proteins, 78(10), 2265-82. PMID: 20544963.

Evans, T. I., Shea, M. A. (2009). Energetics of calmodulin domain interactions with the calmodulin binding domain of CaMKII. Proteins, 76(1), 47-61. PMID: 19089983.

O'Donnell, S. E., Newman, R. A., Witt, T. J., Hultman, R., Froehlig, J. R., Christensen, A. P. & Shea, M. A. (2009). Thermodynamics and conformational change governing domain-domain interactions of calmodulin. Methods in Enzymology, 466, 503-26. PMID: 21609874.

Feldkamp, M. D., Shea, M. A. (2009). Interactions of the Anti-Psychotic Drug Trifluoperazine with Calmodulin. Biophysical Society Meeting.

O'Donnell, S. E., Shea, M. A. (2009). Calcium-Dependent Interactions of Calmodulin with Calcineurin: Evidence of Domain-reversal in Target Recognition. Biophysical Society Meeting.

Newman, R. A., Van Scyoc, W. S., Sorensen, B. R., Jaren, O. R. & Shea, M. A. (2008). Interdomain cooperativity of calmodulin bound to melittin preferentially increases calcium affinity of sites I and II. Proteins, 71(4), 1792-812. PMID: 18175310.

Erickson, J. R., Joiner, M. L., Guan, X., Kutschke, W., Yang, J., Oddis, C. V., Bartlett, R. K., Lowe, J. S., O'Donnell, S. E., Aykin-Burns, N., Zimmerman, M. C., Zimmerman, K., Ham, A. J., Weiss, R. M., Spitz, D. R., Shea, M. A., Colbran, R. J., Mohler, P. J. & Anderson, M. E. (2008). A dynamic pathway for calcium-independent activation of CaMKII by methionine oxidation. Cell, 133(3), 462-74. PMID: 18455987.

Theoharis, N. T., Sorensen, B. R., Theisen-Toupal, J. & Shea, M. A. (2008). The neuronal voltage-dependent sodium channel type II IQ motif lowers the calcium affinity of the C-domain of calmodulin. Biochemistry, 47(1), 112-23. PMID: 18067319.

Feldkamp, M. D., Shea, M. A. (2008). Interactions of the Anti-Psychotic Drug Trifluoperazine with Calmodulin and its effects on Calcium Binding Affinity. (Vols. 94). pp. 1072. Biophysical Journal.

Evans, T., Shea, M. A. (2008). Thermodynamic Selectivity of Calmodulin Binding to Neighboring Sites of L-Type Calcium Channel Cav1.2. (Vols. 94). pp. 476A. Biophysical Journal.

O'Donnell, S. E., Shea, M. A. (2008). Calmodulin and Calcineurin: Mechanisms of Molecular Recognition. (Vols. 94). pp. 1072. Biophysical Journal.

Ataman, Z. A., Gakhar, L., Sorensen, B. R., Hell, J. W. & Shea, M. A. (2007). The NMDA receptor NR1 C1 region bound to calmodulin: structural insights into functional differences between homologous domains. Structure (London, England : 1993), 15(12), 1603-17. PMID: 18073110.

Merrill, M. A., Malik, Z., Akyol, Z., Bartos, J. A., Leonard, A. S., Hudmon, A., Shea, M. A. & Hell, J. W. (2007). Displacement of alpha-actinin from the NMDA receptor NR1 C0 domain By Ca2+/calmodulin promotes CaMKII binding. Biochemistry, 46(29), 8485-97. PMID: 17602661.

Li, Q., Cooper, J. J., Altwerger, G. H., Feldkamp, M. D., Shea, M. A. & Price, D. H. (2007). HEXIM1 is a promiscuous double-stranded RNA-binding protein and interacts with RNAs in addition to 7SK in cultured cells. Nucleic acids research, 35(8), 2503-12. PMID: 17395637.

VanScyoc, W. S., Newman, R. A., Sorensen, B. R. & Shea, M. A. (2006). Calcium binding to calmodulin mutants having domain-specific effects on the regulation of ion channels. Biochemistry, 45(48), 14311-24. PMID: 17128970.

Ross, J., Laws, W. & Shea, M. (2006). Intrinsic fluorescence in protein structure analysis. Protein Structures: Methods in Protein Structure and Structure Analysis: Luinescence Spectroscopy and Circular Dichroism, Nova Science Publishers, Inc (NY), 55-72.

Newman, R. A., Shea, M. A. (2006). Interactions of Calmodulin with Regulatory Regions of the Ryanodine Receptor Type:1 Distinct roles of Domains in Protein Allostery. (Vols. 90). pp. 389A. Biophysical Journal.

Akyol, Z., Gakhar, L., Hell, J. W. & Shea, M. A. (2006). Structure and Mechanism of Calmodulin Binding to a Cell Surface Targeting Region on the N-Methyl-D-aspartate (NMDA) receptor. (Vols. 90). pp. 519A. Biophysical Journal.

Witt, T. J., Newman, R. A. & Shea, M. A. (2006). Allosteric Modulation of Calcium Binding to the N-Domain Sites of Calmodulin. (Vols. 90). pp. 347A. Biophysical Journal.

Evans, T., Shea, M. A. (2006). Domain-Specific Calmodulin Interactions with CaMKII. (Vols. 90). pp. 519A. Biophysical Journal.

Feldkamp, M. D., O'Donnell, S. E. & Shea, M. A. (2006). Allosteric Effects of the Anti-Psychotic Drug Trifluoperazine on Calcium Binding by calmodulin. (Vols. 90). pp. 347A. Biophysical Journal.

Newman, R. A., Shea, M. A. (2005). Energetics and Interfaces of Domain-Specific Binding of Calmodulin to Peptides. (Vols. 88). pp. 85A. Biophysical Journal.

Akyol, Z., Hell, J. W. & Shea, M. A. (2005). Calmodulin Recognition of the NMDA (Glutamate) Receptor. (Vols. 88). pp. 85A. Biophysical Journal.

Theoharis, N., Shea, M. A. (2005). Domain-Specific Binding of Calmodulin to the Neuronal Voltage- Dependent Sodium Channel Type II. Biophysical Journal.

Sorensen, B. R., Shea, M. A. (2005). Domain-Specific Effects on the Thermostability of Calmodulin. (Vols. 88). pp. 214A. Biophysical Journal.

Wang, B., Martin, S. R., Newman, R. A., Hamilton, S. L., Shea, M. A., Bayley, P. M. & Beckingham, K. M. (2004). Biochemical properties of V91G calmodulin: A calmodulin point mutation that deregulates muscle contraction in Drosophila. Protein science : a publication of the Protein Society, 13(12), 3285-97. PMID: 15557269.

Hines, R., Sorensen, B. R., Shea, M. A. & Maury, W. (2004). PU.1 binding to ets motifs within the equine infectious anemia virus long terminal repeat (LTR) enhancer: regulation of LTR activity and virus replication in macrophages. Journal of Virology, 78(7), 3407-18. PMID: 15016863.

Akyol, Z., Bartos, J. A., Merrill, M. A., Faga, L. A., Jaren, O. R., Shea, M. A. & Hell, J. W. (2004). Apo-calmodulin binds with its C-terminal domain to the N-methyl-D-aspartate receptor NR1 C0 region. The Journal of Biological Chemistry, 279(3), 2166-75. PMID: 14530275.

Akyol, Z., Hell, J. W. & Shea, M. A. (2004). Calmodulin Recognition of the NMDA (Glutamate) Receptor. (Vols. 86). pp. 454A. Biophysical Journal.

Newman, R. A., Wang, B., Beckingham, K. & Shea, M. A. (2004). Molecular Basis of Drosophila Hypercontraction Due to Defective Regulation of the Ryanodine Receptor by Calmodulin. (Vols. 86). pp. 238A. Biophysics Journal.

Theoharis, N., Shea, M. A. (2004). Domain-Specific Binding of Calmodulin to the Mammalian Voltage- Dependent Sodium Channel Type II (NAv1.2). (Vols. 86). pp. 453A. Biophysical Journal.

Sorensen, B. R., Shea, M. A. (2004). Domain-Specific Regulation of Calcineurin by Calmodulin. (Vols. 86). pp. 454A. Biophysical Journal.

Faga, L. A., Sorensen, B. R., VanScyoc, W. S. & Shea, M. A. (2003). Basic interdomain boundary residues in calmodulin decrease calcium affinity of sites I and II by stabilizing helix-helix interactions. Proteins, 50(3), 381-91. PMID: 12557181.

Newman, R. A., Hamilton, S. & Shea, M. A. (2003). Domain-specific Interactions of Calmodulin with Ryanodine Receptor Type 1 Regulation. (Vols. 84). pp. 61A. Biophysical Journal.

Sorensen, B. R., Shea, M. A. (2003). Exploring the Role of the Domain Boundary in Allosteric Regulation of Calmodulin. (Vols. 84). pp. 528A. Biophysical Journal.

VanScyoc, W. S., Shea, M. A. (2003). The Molecular Basis for Defective Ion Channel Regulation by Mutants of Calmodulin. (Vols. 84). pp. 61A. Biophysical Journal.

Akyol, Z., Hell, J. & Shea, M. A. (2003). NMDA (Glutamate) Receptor for Recognition by Calmodulin. (Vols. 84). pp. 60A. Biophysical Journal.

Jaren, O. R., Kranz, J. K., Sorensen, B. R., Wand, A. J. & Shea, M. A. (2002). Calcium-induced conformational switching of Paramecium calmodulin provides evidence for domain coupling. Biochemistry, 41(48), 14158-66. PMID: 12450379.

Leonard, A. S., Bayer, K. U., Merrill, M. A., Lim, I. A., Shea, M. A., Schulman, H. & Hell, J. W. (2002). Regulation of calcium/calmodulin-dependent protein kinase II docking to N-methyl-D-aspartate receptors by calcium/calmodulin and alpha-actinin. The Journal of Biological Chemistry, 277(50), 48441-8. PMID: 12379661.

VanScyoc, W. S., Sorensen, B. R., Rusinova, E., Laws, W. R., Ross, J. B. & Shea, M. A. (2002). Calcium binding to calmodulin mutants monitored by domain-specific intrinsic phenylalanine and tyrosine fluorescence. Biophysical Journal, 83(5), 2767-80. PMID: 12414709.

Xiong, L. W., Newman, R. A., Rodney, G. G., Thomas, O., Zhang, J. Z., Persechini, A., Shea, M. A. & Hamilton, S. L. (2002). Lobe-dependent regulation of ryanodine receptor type 1 by calmodulin. The Journal of Biological Chemistry, 277(43), 40862-70. PMID: 12185083.

Sorensen, B. R., Faga, L. A., Hultman, R. & Shea, M. A. (2002). An interdomain linker increases the thermostability and decreases the calcium affinity of the calmodulin N-domain. Biochemistry, 41(1), 15-20. PMID: 11771998.

VanScyoc, W. S., Sorensen, B. R., Rusinova, E., Laws, W. R., Ross, J. B. & Shea, M. A. (2002). Domain-Specific Optical Spectroscopy of Calmodulin: Intrinsic Phenylalanine Fluroscence Selectively Reports on Conformational Change of the N-domain. (Vols. 84). pp. A1608. Biophysical Journal.

Sorensen, B. R., Coffeen, L. A., Hultman, R. & Shae, M. A. (2002). Linker Residues Stabilize Calmodulin N-domain and reduce its Calcium Affinity. (Vols. 82). pp. A1610. Biophysical Journal.

Shea, M. A., Newman, R. A., Akyol, Z., Volokhina, Y. & Sorensen, B. R. (2002). Thermodynamic Properties and Calcium-induced Structural Changes of Paramecium Calmodulin Mutants Defective in K+ Channel Regulation. (Vols. 82). pp. A1609. Biophysical Journal.

VanScyoc, W. S., Shea, M. A. (2001). Phenylalanine fluorescence studies of calcium binding to N-domain fragments of Paramecium calmodulin mutants show increased calcium affinity correlates with increased disorder. Protein science : a publication of the Protein Society, 10(9), 1758-68. PMID: 11514666.

Sun, H., Yin, D., Coffeen, L. A., Shea, M. A. & Squier, T. C. (2001). Mutation of Tyr138 disrupts the structural coupling between the opposing domains in vertebrate calmodulin. Biochemistry, 40(32), 9605-17. PMID: 11583160.

Sorensen, B. R., Eppel, J. T. & Shea, M. A. (2001). Paramecium calmodulin mutants defective in ion channel regulation associate with melittin in the absence of calcium but require it for tertiary collapse. Biochemistry, 40(4), 896-903. PMID: 11170410.

Jaren, O. R., Kranz, J. K., Sorensen, B. R., Wand, A. J. & Shea, M. A. (2001). Calcium-Dependent Conformational Switching of Paramecium Calmodulin: Observation of Changes in the Protein Backbone by NMR. (Vols. 80). pp. 899A. Biophysical Journal.

VanScyoc, W. S., Coffeen, L. A. & Shea, M. A. (2001). Structure, Stability, and Calcium Binding Properties of Mutants of Paramecium Calmodulin Defective in Ion Channel Regulation. (Vols. 80). pp. 317A. Biophysical Journal.

Sorensen, B. R., VanScyoc, W., Eppel, J. T. & Shea, M. A. (2001). Calcium dependent Melittin Binding to Paramecium Calmodulin is Domain-Specific and Altered by Mutations. (Vols. 80). pp. A1301. Biophysical Journal.

Squier, T. C., Sun, H., Yin, D., Coffeen, L. A., Jaren, O. R. & Shea, M. A. (2001). Tyr138 Mediates the Structural Coupling Between the Opposing Domains in Vertebrate Calmodulin. (Vols. 80). pp. A457. Biophysical Journal.

Jaren, O. R., Harmon, S., Chen, A. F. & Shea, M. A. (2000). Paramecium calmodulin mutants defective in ion channel regulation can bind calcium and undergo calcium-induced conformational switching. Biochemistry, 39(23), 6881-90. PMID: 10841769.

Shea, M. A., Sorensen, B. R., Pedigo, S. & Verhoeven, A. S. (2000). Proteolytic footprinting titrations for estimating ligand-binding constants and detecting pathways of conformational switching of calmodulin. Methods in enzymology, 323, 254-301. PMID: 10944756.

Jaren, O., Coffeen, L. & Shea, M. A. (2000). Mutations between calcium binding sites I and II alter interdomain anticooperativity of calmodulin. (Vols. 78). pp. 151A.

Jaren, O., Chen, A. & Shea, M. A. (1999). Calcium-Saturated Paramecium Calmodulin Mutants Retain Normal Properties. (Vols. 76). pp. A01. Biophysical Journal.

Sorensen, B. R., Shea, M. A. (1998). Interactions between domains of apo calmodulin alter calcium binding and stability. Biochemistry, 37(12), 4244-53. PMID: 9521747.

Shea, M. A., Sorensen, B. R. (1998). Calmodulin Domain Interactions: Nonadditivity in Calcium Binding and Stability. (Vols. 74). pp. A39. Biophysical Journal.

Sorensen, B. R., Shea, M. A. (1997). Hydrodynamic and Proteolytic Footprinting Studies of Calcium Induced Interdomain Interactions in Calmodulin. (Vols. 72). pp. A76. Biophysical Journal.

Sorensen, B. R., Shea, M. A. (1996). Calcium binding decreases the stokes radius of calmodulin and mutants R74A, R90A, and R90G. Biophysical journal, 71(6), 3407-20. PMID: 8968610.

Shea, M. A., Verhoeven, A. S. & Pedigo, S. (1996). Calcium-induced interactions of calmodulin domains revealed by quantitative thrombin footprinting of Arg37 and Arg106. Biochemistry, 35(9), 2943-57. PMID: 8608132.

Pedigo, S., Shea, M. A. (1995). Discontinuous equilibrium titrations of cooperative calcium binding to calmodulin monitored by 1-D 1H-nuclear magnetic resonance spectroscopy. Biochemistry, 34(33), 10676-89. PMID: 7654722.

Pedigo, S., Shea, M. A. (1995). Quantitative endoproteinase GluC footprinting of cooperative Ca2+ binding to calmodulin: proteolytic susceptibility of E31 and E87 indicates interdomain interactions. Biochemistry, 34(4), 1179-96. PMID: 7827068.

Harmon, S. D., Shea, M. A. (1995). Allosteric Disruption of Paramecium Calmodulin. (Vols. 68). Biophysical Journal.

Pedigo, S., Shea, M. A. (1995). Energetics of Calcium Binding to Calmodulin. (Vols. 68). Biophysical Journal.

Sorensen, B. R., Shea, M. A. (1995). Mutational Perturbation of Calmodulin Structure. (Vols. 68). Biophysical Journal.

Daugherty, M. A., Shea, M. A. & Ackers, G. K. (1994). Bohr effects of the partially-ligated (CN-met) intermediates of hemoglobin as probed by quaternary assembly. Biochemistry, 33(34), 10345-57. PMID: 8068671.

Pedigo, S., Shea, M. A. (1994). Equilibrium Ca2+ Titrations of Calmodulin Monitored by NMR. (Vols. 66). Biophysical Journal.

Harmon, S. D., Shea, M. A. (1994). Ion Binding Properties and Conformations of Flagellar Calcium Binding Protein. (Vols. 66). Biophysical Journal.

Daughtery, M. A., Shea, M. A. (1993). Bohr Effects of the Partially-Ligated Microstates of Human Hemoglobin. (Vols. 64). (2) Biophysical Journal.

Verhoeven, A. S., Shea, M. A. (1993). Ca2+- Induced Domain Interactions of Calmodulin. (Vols. 64). Biophysical Journal.

Koblan, K. S., Bain, D. L., Beckett, D., Shea, M. A. & Ackers, G. K. (1992). Analysis of site-specific interaction parameters in protein-DNA complexes. Methods in enzymology, 210, 405-25. PMID: 1584044.

Schaller, W. A., Shea, M. A. (1992). Conformational Changes in Calmodulin. (Vols. 61). pp. 211a. Biophysical Journal.

Pedigo, S., Kephart, C. R. & Shea, M. A. (1992). Cooperative Calcium Binding by Calmodulin as Probed by Endorproteinase Glu C. (Vols. 61). pp. 211a. Biophysical Journal.

Daugherty, M. A., Shea, M. A., Johnson, J. A., LiCata, V. J., Turner, G. J. & Ackers, G. K. (1991). Identification of the intermediate allosteric species in human hemoglobin reveals a molecular code for cooperative switching. Proceedings of the National Academy of Sciences of the United States of America, 88(4), 1110-4. PMID: 1996311.

Pedigo, S., Verhoeven, A. S., Schaller, W. A. & Shea, M. A. (1991). Ligand-linked Conformational Changes of Calmodulin. (Vols. 59). pp. 23a. Biophysical Journal.

Daughtery, M. A., Shea, M. A. & Ackers, G. K. (1991). Effects of protons on the energetics of cooperativity of the intermediate allosteric species of human hemoglobin. (Vols. 59). pp. 109a. Biophysical Journal.

Shea, M. A., Pedigo, S., Schaller, W. A. & Verhoeven, A. S. (1991). Ligand-linked Conformational Changes of Calmodulin. (Vols. 15G). pp. 200. Journal of Cellular Biochemistry.

Perrella, M., Benazzi, L., Shea, M. A. & Ackers, G. K. (1990). Subunit hybridization studies of partially ligated cyanomethemoglobins using a cryogenic method. Evidence for three allosteric states. Biophysical chemistry, 35(1), 97-103. PMID: 2328279.

Shea, M. A., Ackers, G. K. (1989). Cooperative Interactions of Human Hemoglobin- Partially ligated Species respond differently to protons. (Vols. 55). pp. 345. Biophysical Journal.

Senear, D. F., Brenowitz, M., Shea, M. A. & Ackers, G. K. (1986). Energetics of cooperative protein-DNA interactions: comparison between quantitative deoxyribonuclease footprint titration and filter binding. Biochemistry, 25(23), 7344-54. PMID: 3026451.

Brenowitz, M., Senear, D. F., Shea, M. A. & Ackers, G. K. (1986). Footprint titrations yield valid thermodynamic isotherms. Proceedings of the National Academy of Sciences of the United States of America, 83(22), 8462-6. PMID: 3464963.

Brenowitz, M., Senear, D. F., Shea, M. A. & Ackers, G. K. (1986). Quantitative DNase footprint titration: a method for studying protein-DNA interactions. Methods in Enzymology, 130(part K), 132-81. PMID: 3773731.

Shea, M. A., Ackers, G. K. (1985). The OR control system of bacteriophage lambda. A physical-chemical model for gene regulation. Journal of Molecular Biology, 181(2), 211-30. PMID: 3157005.

Ackers, G. K., Shea, M. A. & Smith, F. R. (1983). Free energy coupling within macromolecules. The chemical work of ligand binding at the individual sites in co-operative systems. Journal of Molecular Biology, 170(1), 223-42. PMID: 6631962.

Shea, M. A., Ackers,, G. K. (1983). Dynamics of gene regulation in the QR/OL control system of bacteriophage lambda. Mobility and Recognition in Cell Biology, Walter de Gruyter, Berlin, 328-343.

Ackers, G. K., Johnson, A. D. & Shea, M. A. (1982). Quantitative model for gene regulation by lambda phage repressor. Proceedings of the National Academy of Sciences of the United States of America, 79(4), 1129-33. PMID: 6461856.