Thrombin-Thrombomodulin

White, C. E., Hunter, M. J., Meininger, D. P., White, L. R. & Komives, E. A. (1995) ““Large Scale Expression, Purification and Characterization of the Smallest Active Fragment of Thrombomodulin: The Roles of the Sixth Domain and of Methionine-388” Protein Engineering 8, 1177 – 1187.

White, CE; Hunter, MJ; Meininger, DP; Garrod, S; Komives, EA. The fifth epidermal growth factor-like domain of thrombomodulin does not have an epidermal growth factor-like disulfide bonding pattern. Proceedings of the National Academy of Sciences of the United States of America, 1996 Sep 17, 93(19):10177-82.

Sampoli Benitez, BA; Hunter, MJ; Meininger, DP; Komives, EA. Structure of the fifth EGF-like domain of thrombomodulin: An EGF-like domain with a novel disulfide-bonding pattern.” Journal of Molecular Biology, 1997 Nov 7, 273(4):913-26.

Wood, M. J., Sampoli Benitez, B., Komives, E. A. Solution structure of the smallest cofactor-active fragment of thrombomodulin. Nature Structural Biology, 2000 Mar, 7(3):200-4.

Sampoli Benitez, B.& Komives, E. A. (2000) “Disulfide bond plasticity in EGF” Proteins, Structure, Function and Genetics 40, 168 – 174.

Baerga-Ortiz, A. J., Rezaie, A. R. & Komives, E. A. (2000) “Electrostatic Dependence of the Thrombin-Thrombomodulin interaction” J. Mol. Biol. 296: 651 – 658.

Mandell, J. G. Baerga-Ortiz, A., Akashi, S., Takio, K. & Komives, E. A. (2001) “Solvent Accessibility of the Thrombin-Thrombomodulin Interface” J. Mol. Biol. 306, 575-589.

Baerga-Ortiz, A., Hughes, C. A., Mandell, J. G. & Komives, E. A. (2002) “Epitope Mapping of a monoclonal antibody against human thrombin by H/D exchange mass spectrometry reveals selection of a diverse sequence in a highly conserved protein” Protein Science 11, 1300-1308.

Wood, M. J., Becvar, L. A., Prieto, J. H., Melacini, G., & Komives, E. A. (2003) NMR Structures Reveal How Oxidation Inactivates Thrombomodulin Biochemistry 42, 11932-42.

Baerga-Ortiz, A., Bergqvist, S. P., Mandell, J. G. & Komives, E. A. (2004) “Two different proteins that compete for binding to thrombin have opposite kinetic and thermodynamic profiles” Protein Science 13, 166-176.

Croy, C.H., Koeppe, J.R., Bergqvist, S., Komives, E.A.(2004) “Allosteric changes in solvent accessibility observed in thrombin upon active site occupation.” Biochemistry 43, 5246-55.

Prieto, J. H., Sampoli Benitez, B., Melacini, G., Johnson, D. A., Wood, M. J., & Komives, E. A. (2005) Dynamics of the Fragment of Thrombomodulin Containing the Fourth and Fifth EGF-Like Domains Correlate with FunctionBiochemistry 44, 1225-1235.

Koeppe, J. R., Seitova, A., Mather, T., Komives, E. A. (2005) “Thrombomodulin tightens the thrombin active site loops to promote protein C activation.” Biochemistry 44, 14784-91.

Wood, M. J., Prieto, J. H. & Komives, E. A. (2005) Structural and functional consequences of methionine oxidation in thrombomodulin Biochim. Biophys. Acta 1703, 141-147.

Koeppe, J. R. and Komives, E. A. (2006) “Amide H/2H Exchange Reveals a Mechanism of Thrombin Activation.” Biochemistry 45, 7724-32.

Koeppe, J. R., Beach, M.S. and Komives, E. A. (2008) “Mutations in the fourth EGF-like domain affect thrombomodulin-induced changes in the active site of thrombin.” Biochemistry 47, 10933-39.

Treuheit, NA, Beach, MA. and Komives, EA. (2011) Thermodynamic compensation upon binding to exosite 1 and the active site of thrombin. Biochemistry 50, 4590-6. PMC3107735

Fuglestad B, Gasper PM, Tonelli M, McCammon JA, Markwick PR, Komives EA. (2012) The dynamic structure of thrombin in solution. Biophys J. 103(1):79-88. PMC3388214

Gasper, PM, Fuglestad, B., Komives, EA, Markwick, PRL, McCammon, JA. (2012) Allosteric networks in thrombin distinguish procoagulant and anticoagulant activities. Proc Natl Acad Sci USA 109(52):21216-22. PMC3535651

Fuglestad B, Gasper PM, McCammon JA, Markwick PR, Komives EA. (2013) Correlated Motions and Residual Frustration in Thrombin. J Phys Chem B. 117(42):12857-63 PMC3808083

Boechi L, Pierce L, Komives EA, McCammon JA. (2014)Trypsinogen activation as observed in accelerated molecular dynamics simulations.Protein Sci. 2014 Nov;23(11):1550-8. PMC4241106

Handley LD, Treuheit NA, Venkatesh VJ, Komives EA. (2015)Thrombomodulin Binding Selects the Catalytically Active Form of Thrombin Biochemistry 54(43):6650-8. PMC4697735

Handley, LD, Fuglestad, B, Stearns, K, Tonelli, M, Fenwick, RB, Markwick, PRL, and Komives, EA (2017) NMR reveals a dynamic allosteric pathway in thrombin. Scientific Reports 7:39575. PMC5216386

NFκB-IκBα

Croy, C. H, Bergqvist, S. P., Huxford, T., Ghosh, G. & Komives, E. A. (2004) Biophysical characterization of the free IkappaBalpha ankyrin repeat domain in solution. Protein Sci. 13, 1767-77.

Ferreiro, D. U., Cho, S. S. Komives, E. A.& Wolynes, P. G. (2005) The energy landscape of modular repeat proteins: Topology determines folding mechanism in the ankyrin family J. Mol. Biol. 354, 679-92.

Bergqvist, S., Croy, C. H., Kjaergaard, M., Huxford, T., Ghosh, G. & Komives, E. A. (2006) Thermodynamics reveal that helix four in the NLS of NF-kappaB p65 anchors IkappaBalpha, forming a very stable complex. J. Mol. Biol. 360, 421-34.

Truhlar, S. M. E., Torpey, J. W., & Komives, E. A. (2006) Regions of IkappaBalpha that are critical for its inhibition of NF-kappaB-DNA interaction fold upon binding to NF-kappaB. Proc. Nat. Acad. Sci. U. S. A. 103, 18951-6.

Ferreiro, D. U., Cervantes, C. F., Truhlar, S. M. E., Cho, S. S., Wolynes, P. G., Komives, E. A. (2006) Stabilizing IkappaBalpha by consensus design. J. Mol. Biol. 365, 1201-16.

Latzer, J., Papoian, G. A., Prentiss, M. C., Komives, E. A., Wolynes, P. G. (2007) Induced fit, folding, and recognition of the NF-kappaB-nuclear localization signals by IkappaBalpha and IkappaBbeta. J Mol Biol. 367, 262-74.

Ferreiro, D. U., Hegler, J. A., Komives, E. A. and Wolynes, P. G. (2007) Localizing Frustration in native proteins and protein assemblies. Proc. Nat. Acad. Sci. U. S. A. 104, 19819-24.

Barrick, D., Ferreiro, D. U., Komives, E. A. (2008) Folding landscapes of ankyrin repeat proteins: experiments meet theory. Curr. Opp. Struct. Biol. 18, 27-34.

Truhlar, S. M. E., Mathes, E., Cervantes, C. F., Ghosh, G., Komives, E. A. (2008) Pre-folding IkBa alters control of NF-kB signaling. J. Mol. Biol. 380, 67-82.

Ferreiro, D.U., Walczak, A. M., Komives, E. A. and Wolynes, P. G. (2008) The energy landscapes of repeat-containing proteins: topology, cooperativity, and the folding funnels of one-dimensional architectures. PLoS Comput Biol. 16, 4(5):e1000070.

Bergqvist, S., Ghosh, G. & Komives, E. A. (2008) The IkappaBalpha/NF-kappaB complex has two hot spots, one at either end of the interface. Prot. Sci. 17, 2051-8.

Bergqvist, S., Alverdi, V., Mengel, B., Hoffmann, A., Ghosh, G., Komives, E. A. (2009) Kinetic enhancement of NF-kB-DNA dissociation by IkBa Proc. Nat. Acad. Sci. U. S. A., 106, 19328-33.

Cervantes, C. F., Markwick, P. R. L., Sue, S. C., McCammon, J. A., Dyson, H. J., Komives, E. A. (2009)Functional dynamics of the folded ankyrin repeats of IkappaB alpha revealed by nuclear magnetic resonance.Biochemistry 48, 8023-31. PMC2728578

Markwick, P. R., Cervantes, C. F., Abel, B. L., Komives, E. A., Blackledge, M. , McCammon, J. A. (2010)Enhanced conformational space sampling improves the prediction of chemical shifts in proteins. J Am Chem Soc. 132, 1220-1.PMC2812018

Ferreiro, D. U., Komives, E.A. (2010) Molecular Mechanisms of System Control of NF-kappaB Signaling by IkappaBalpha. Biochemistry 49, 1560-7. PMC2865148

Mathes E, Wang L, Komives E, Ghosh G. (2010) Flexible regions within IkappaBalpha create the ubiquitin-independent degradation signal. J Biol Chem. 285, 32927-36. PMCID: PMC2963393.

Devries, I., Hampton-Smith, R. J., Mulvihill, M., Alverdi, V., Peet, D. J., and Komives, E. A., (2010)Consequences of IkappaB alpha hydroxylation by the factor inhibiting HIF (FIH). FEBS Lett. 584, 4725-30. PMC3034650.

Cervantes, C. F., Bergqvist, S., Kjaergaard, M., Kroon, G., Sue, S-C., Dyson, H. J., and Komives, E. A. (2010)The RelA nuclear localization signal folds upon binding to IkBa. J Mol Biol 405, 754-64. PMC3056351

Sue SC, Alverdi V, Komives EA, Dyson HJ. (2011) Detection of a ternary complex of NF-kappaB and IkappaBalpha with DNA provides insights into how IkappaBalpha removes NF-kappaB from transcription sites.Proc Natl Acad Sci U S A. 108, 1367-72. PMC3029698.

Devries, I., Ferreiro, D. U., Sánchez, I. E. and Komives, E. A. (2011) Folding Kinetics of the Cooperatively Folded Subdomain of the IκBα Ankyrin Repeat Domain. J. Mol. Biol. 408, 163-76. PMC3081522

Lamboy, J. A., Kim, H., Lee, K. S., Ha, T. and Komives, E. A. (2011) P Visualization of the nanospring dynamics of the IκBα ankyrin repeat domain in real time roc. Nat. Acad. Sci. U S A. 108, 10178-83. PMC3121830

Komives EA. (2012) Consequences of Fuzziness in the NFκB/IκBα Interaction. Adv Exp Med Biol. 725:74-85. PMC3603378

Dyson HJ, Komives EA. (2012) Role of disorder in IkB-NFkB interaction. IUBMB Life 64(6):499-505. doi: 10.1002/iub.1044. PMC3575514

Schafer NP, Hoffman RM, Burger A, Craig PO, Komives EA, Wolynes PG. (2012) Discrete kinetic models from funneled energy landscape simulations. PLoS One. 2012;7(12):e50635. doi: 10.1371/journal.pone.0050635. PMC3520928

Cervantes CF, Handley LD, Sue SC, Dyson HJ, Komives EA. (2013) Long-range effects and functional consequences of stabilizing mutations in the ankyrin repeat domain of IκBα J Mol Biol. 425(5):902-13. PMC3744861

Lamboy-Gonzalez, J., Kim, H., Dembinski, H., Ha, T.J., Komives, E. A. (2013) Single molecule FRET reveals the native state dynamics of the IκBα ankyrin repeat domain. J Mol Biol. 425(14):2578-90. PMC3758917

Dembinski H, Wismer K, Balasubramaniam D, Gonzalez HA, Alverdi V, Iakoucheva LM, Komives EA. (2014)Predicted disorder-to-order transition mutations in IκBα disrupt function. Phys Chem Chem Phys. 16(14):6480-5. PMC4040282

Alverdi V, Hetrick B, Joseph S, Komives EA. Direct observation of a transient ternary complex during IκBα-mediated dissociation of NF-κB from DNA. Proc Nat Acad Sci 111(1):225-30. PMC3890772

Ferreiro DU, Komives EA, Wolynes PG. (2014) Frustration in Biomolecules Q Rev Biophys. 2014 Nov;47(4):285-363. PMC4256721

Potoyan DA, Zheng W, Komives EA, Wolynes PG. (2016) Molecular stripping in the NF-κB/IκB/DNA genetic regulatory network. Proc Natl Acad Sci U S A. 113(1):110-115. PMC4711861

Trelle MB, Ramsey KM, Lee TC, Zheng W, Lamboy J, Wolynes PG, Deniz A, Komives EA. (2016) Binding of NFκB Appears to Twist the Ankyrin Repeat Domain of IκBα. Biophys J. 110(4):887-95. PMC4776026

Potoyan DA, Zheng W, Ferreiro DU, Wolynes PG, Komives EA. (2016) PEST Control of Molecular Stripping of NFκB from DNA Transcription Sites. J Phys Chem B. 120(33):8532-8538.

Dembinski, HD, Wismer, K, Vargas, JD, Suryawanshi, GW, Kern, N, Kroon, GJA, Dyson, HJ, Hoffmann, A, Komives, EA (2017) Functional importance of stripping in NFκB signaling revealed by a stripping-impaired IκBα mutant. Proc Natl Acad Sci U S A 114, 1916-1921. PMC5338396

Ramsey KM, Dembinski HE, Chen W, Ricci CG, Komives EA. (2017) DNA and IκBα Both Induce Long-Range Conformational Changes in NFκB. J Mol Biol. 429(7):999-1008. PMC5389416

Mass Spectrometry

Mandell, JG; Falick, AM; Komives, EA. Measurement of amide hydrogen exchange by MALDI-TOF mass spectrometry. Analytical Chemistry, 1998 Oct 1, 70(19):3987-95.

Mandell, JG; Falick, AM; Komives, EA. Identification of protein-protein interfaces by decreased amide proton solvent accessibility. Proceedings of the National Academy of Sciences of the United States of America, 1998 Dec 8, 95(25):14705-10.

Mandell, JG; Baerga-Ortiz, Komives, EA.(2001) Solvent accessibility of the thrombin-thrombomodulin interface.J. Mol. Biol. 306: 575-589.

Hughes, C. A., Mandell, J. G., Anand, G. S., Stock, A. M. & Komives, E. A. (2001) Phosphorylation Causes Subtle Changes in Solvent Accessibility at the Interdomain Interface of Methylesterase CheB J. Mol. Biol. 307, 967-976.

Baerga-Ortiz, A; Hughes, CA; Mandell, JG; Komives, EA. (2002) Epitope mapping of a monoclonal antibody against human thrombin by H/D exchange mass spectrometry reveals selection of a diverse sequence in a highly conserved protein. Protein Sci 11, 1300-1308.

Anand, G. S., Hughes, C. A., Jones, J. M., Taylor, S. S. & Komives, E. A. (2002) Amide H/2H exchange reveals communication between the cAMP- and catalytic subunit-binding sites in the regulatory subunit of protein kinase A. J. Mol. Biol. 323, 377-386.

Anand, G. S., Law, D., Mandell, J. G., Snead, A. N., Tsigelny, I., Taylor, S. S., Ten Eyck, L., & Komives, E. A. (2003) Identification of the Protein Kinase A Regulatory RI -Catalytic Subunit Interface by Amide H/2H Exchange and Protein Docking Proc. Nat. Acad. Sci. U. S. A. 100, 13264-13269.

Komives, E. A.(2005) Protein-protein interaction dynamics by amide H/2H exchange mass spectrometryInternational Journal of Mass Spectrometry 240, 285-290.

Hotchko, M., Anand, G., Komives, E. A., & Ten Eyck, L. (2006) Automated extraction of backbone deuteration levels from amide H/2H exchange mass spectrometry experiments Protein Science 15, 583 – 601.

Truhlar, S. M. E., Croy, C. H., Torpey, J. W., Koeppe, J. R. & Komives, E. A. (2006) Solvent Accessibility of Protein Surfaces by Amide H/2H Exchange MALDI-TOF Mass Spectrometry. J. Am. Soc. Mass Spectrom. 17, 1490 – 97.

Anand, G. S., Hotchko, M., Brown, S. H., Ten Eyck, L. F., Komives, E. A. and Taylor, S. S. (2007) R-subunit Isoform Specificity in Protein Kinase A: Distinct Features of Protein Interfaces in PKA Types I and II by Amide H/(2)H Exchange Mass Spectrometry. J Mol Biol. 374, 487-99.

Gertsman, I., Gan, L., Guttman, M., Lee, K., Duda, R. L., Hendrix, R. W., Komives, E. A., Johnson, J. E. (2009)An unexpected twist in viral capsid maturation Nature 458, 646-50.PMC2765791

Gertsman, I., Komives, E. A., Johnson, J. E. (2010) HK97 Maturation Studied by Crystallography and H/(2)H Exchange Reveals the Structural Basis for Exothermic Particle Transitions. J Mol Biol. 397, 560-574. PMC2938056.

Gertsman, I., Fu, C., Huang, R., Komives, E. A., Johnson, J. E. (2010) Critical salt bridges guide capsid assembly, stability, and maturation behavior in Bacteriophage HK97. Mol Cell Proteomics 9, 1752-63. PMC2938056.

Craig PO, Lätzer J, Weinkam P, Hoffman RM, Ferreiro DU, Komives EA, Wolynes PG. (2011) Prediction of native-state hydrogen exchange from perfectly funneled energy landscapes. J Am Chem Soc. 133(43):17463-72. PMC3203634

Meyer JG, Komives EA. (2012) Charge state coalescence during electrospray ionization improves peptide identification by tandem mass spectrometry. J Am Soc Mass Spec 23, 1390-1399. doi: 10.1007/s13361-012-0404-0.

Balasubramaniam D, Komives EA. (2012) Hydrogen-exchange mass spectrometry for the study of intrinsic disorder in proteins. Biochim Biophys Acta. doi:pii: S1570-9639(12)00250-6. 10.1016/j.bbapap.2012.10.009. PMC3600394

Ramirez-Sarmiento C, Baez M, Wilson CAM, Babul J, Komives EA, Guixé V. (2013) Observation of solvent penetration during cold denaturation of E. coli phosphofructokinase-2. Biophys J 104, 2254-2263.

Meyer JG, Kim S, Maltby DA, Ghassemian M, Bandeira N, Komives EA. (2014) Expanding proteome coverage with orthogonal-specificity α-lytic proteases. Mol Cell Proteomics 13(3):823-35.

Ramírez-Sarmiento CA, Baez M, Zamora RA, Balasubramaniam D, Babul J, Komives EA, Guixé V. (2015) The folding unit of phosphofructokinase-2 as defined by the biophysical properties of a monomeric mutant. Biophys J 108(9):2350-61

Ankyrin and SOCS Box Proteins

Balasubramaniam D, Schiffer J, Parnell J, Mir SP, Amaro RE, Komives EA. (2015) How the ankyrin and SOCS box protein, ASB9, binds to creatine kinase. Biochemistry 54(8):1673-80.

Schiffer JM, Malmstrom RD, Parnell J, Ramirez-Sarmiento C, Reyes J, Amaro RE, Komives EA (2016) Model of the Ankyrin and SOCS Box Protein, ASB9, E3 Ligase Reveals a Mechanism for Dynamic Ubiquitin Transfer. Structure 2;24(8):1248-56). PMC4972691

Other Projects

The LDL receptor-related protein

Mentz, S., DeLacalle, S. Baerga-Ortiz, A. J., Knauer, M. F., Knauer, D. J. & Komives, E. A. (1999)
Mechanism of thrombin clearance by human astrocytoma cells.
J. Neurochemistry 72, 980-987.

Croy, J. E., Shin, W. D., Knauer, M. F., Knauer, D. J., & Komives, E. A. (2003) All three LDL receptor homology regions of the LDL receptor-related protein (LRP) bind multiple ligands. Biochemistry 42, 13049-57.

Croy, J. E., Brandon, T. & Komives, E. A. (2004) Two apolipoprotein E mimetic peptides, apoE(130-149) and apoE(141-155)2, bind to LRP1. Biochemistry 43, 7328-35.

Betts, G. N, van der Geer, P. & Komives, E. A. (2008) Structural and Functional Consequences of Tyrosine Phosphorylation in the LRP1 Cytoplasmic Domain. J Biol Chem. 283, 15656-64.

Guttman, M., Prieto, J. H., Croy, J. E. & Komives, E. A. (2010) Decoding of Lipoprotein-Receptor Interactions: Properties of Ligand Binding Modules Governing Interactions with Apolipoprotein E Biochemistry 49, 1207-1216.

Guttman, M., Betts, G. N, Barnes, H., Ghassemian, M., Van der geer, P. & Komives, E. A. (2009) Interactions of the NPXY microdomains of the low density lipoprotein receptor-related protein 1 Proteomics, 9, 5016-5028.

Guttman, M., Prieto, J. H., Handel. T. M., Domaille, P. J. & Komives, E. A. (2010) Structure of the Minimal Interface Between ApoE and LRP J. Mol. Biol., 398, 306-319.

Mulvihill, M, Guttman, M. and Komives EA (2011) Protein Interactions among Fe65, the Low-Density Lipoprotein Receptor-Related Protein, and the Amyloid Precursor Protein Biochemistry 50(28):6208-16. PMC3139566

Guttman, M. and Komives, EA (2011) Structure, dynamics and binding of the LA45 module pair of the Low Density Lipoprotein Receptor suggest an important role for LA4 in ligand release. Biochemistry 50(51):11001-8. PMC3263374

Pichia Pastoris Expression

White, C. E., Hunter, M. J., Meininger, D. P., White, L. R. & Komives, E. A. (1995) Large Scale Expression, Purification and Characterization of the Smallest Active Fragment of Thrombomodulin: The Roles of the Sixth Domain and of Methionine-388 Protein Engineering 8, 1177 – 1187.

Gleeson, M.A. G., White. C. E., Meininger, D. P. & Komives, E. A. (1997) Generation of Protease Deficient Strains of Pichia pastoris and Their Use in Heterologous Protein Expression Methods in Molecular Biology 103, 81 – 94.

Greenwald, J., Le, V., Corrigan, A., Fischer, W., Komives, E., Vale, W., Choe, S. (1998) Characterization of the extracellular ligand-binding domain of the type II activin receptor. Biochemistry 37, 16711 – 16718.

Wood, M. J. & Komives, E. A. (1999) Production of Large Quantities of Isotopically-Labeled Protein in Pichia pastoris by Fermentation J. Biomolecular NMR 13, 149 – 159.