Differences in the dynamics of the tandem-SH2 modules of the Syk and ZAP-70 tyrosine kinases

Hobbs, Helen T.; Shah, Neel H.; Badroos, Jean M.; Gee, Christine L.; Marqusee, Susan; Kuriyan, John

doi:10.1002/pro.4199

Differences in the dynamics of the tandem-SH2 modules of the Syk and ZAP-70 tyrosine kinases

Journal Article · Sun Oct 03 00:00:00 EDT 2021 · Protein Science

DOI:https://doi.org/10.1002/pro.4199· OSTI ID:2470656

^[1]; Shah, Neel H. ^[2]; Badroos, Jean M. ^[3]; ^[4]; ^[5]; Kuriyan, John ^[5]

University of California, Berkeley, CA (United States); Univ. of California, Irvine, CA (United States)
University of California, Berkeley, CA (United States); Howard Hughes Medical Institute, Berkeley, CA (United States); Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States); Columbia Univ., New York, NY (United States)
Department of Molecular and Cell Biology University of California Berkeley California USA
University of California, Berkeley, CA (United States); Howard Hughes Medical Institute, Berkeley, CA (United States)
University of California, Berkeley, CA (United States); Howard Hughes Medical Institute, Berkeley, CA (United States); Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

The catalytic activity of Syk-family tyrosine kinases is regulated by a tandem Src homology 2 module (tSH2 module). In the autoinhibited state, this module adopts a conformation that stabilizes an inactive conformation of the kinase domain. The binding of the tSH2 module to phosphorylated immunoreceptor tyrosine-based activation motifs necessitates a conformational change, thereby relieving kinase inhibition and promoting activation. We determined the crystal structure of the isolated tSH2 module of Syk and find, in contrast to ZAP-70, that its conformation more closely resembles that of the peptide-bound state, rather than the autoinhibited state. Hydrogen–deuterium exchange by mass spectrometry, as well as molecular dynamics simulations, reveal that the dynamics of the tSH2 modules of Syk and ZAP-70 differ, with most of these differences occurring in the C-terminal SH2 domain. Our data suggest that the conformational landscapes of the tSH2 modules in Syk and ZAP-70 have been tuned differently, such that the autoinhibited conformation of the Syk tSH2 module is less stable. This feature of Syk likely contributes to its ability to more readily escape autoinhibition when compared to ZAP-70, consistent with tighter control of downstream signaling pathways in T cells.

View Accepted Manuscript (DOE)

Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: USDOE; National Institutes of Health (NIH)

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 2470656

Journal Information:: Protein Science, Journal Name: Protein Science Journal Issue: 12 Vol. 30; ISSN 0961-8368

Publisher:: Wiley -- The Protein SocietyCopyright Statement

Country of Publication:: United States

Language:: English

References (32)

The Syk protein tyrosine kinase can function independently of CD45 or Lck in T cell antigen receptor signaling. Chu, D. H.; Spits, H.; Peyron, J. F. The EMBO Journal, Vol. 15, Issue 22 https://doi.org/10.1002/j.1460-2075.1996.tb01015.x	journal	November 1996
Entropic allostery dominates the phosphorylation‐dependent regulation of Syk tyrosine kinase release from immunoreceptor tyrosine‐based activation motifs Feng, Chao; Roy, Amitava; Post, Carol Beth Protein Science, Vol. 27, Issue 10 https://doi.org/10.1002/pro.3489	journal	October 2018
Structural basis for syk tyrosine kinase ubiquity in signal transduction pathways revealed by the crystal structure of its regulatory SH2 domains bound to a dually phosphorylated ITAM peptide Fütterer, Klaus; Wong, Jane; Grucza, Richard A. Journal of Molecular Biology, Vol. 281, Issue 3 https://doi.org/10.1006/jmbi.1998.1964	journal	August 1998
T-coffee: a novel method for fast and accurate multiple sequence alignment 1 1Edited by J. Thornton Notredame, Cédric; Higgins, Desmond G.; Heringa, Jaap Journal of Molecular Biology, Vol. 302, Issue 1 https://doi.org/10.1006/jmbi.2000.4042	journal	September 2000
ConSurf: an algorithmic tool for the identification of functional regions in proteins by surface mapping of phylogenetic information Armon, Aharon; Graur, Dan; Ben-Tal, Nir Journal of Molecular Biology, Vol. 307, Issue 1 https://doi.org/10.1006/jmbi.2000.4474	journal	March 2001
Signal transduction by lymphocyte antigen receptors Weiss, Arthur; Littman, Dan R. Cell, Vol. 76, Issue 2 https://doi.org/10.1016/0092-8674(94)90334-4	journal	January 1994
The Conformational Plasticity of Protein Kinases Huse, Morgan; Kuriyan, John Cell, Vol. 109, Issue 3 https://doi.org/10.1016/S0092-8674(02)00741-9	journal	May 2002
Mechanisms and uses of hydrogen exchange Englander, S. Walter; Sosnick, Tobin R.; Englander, Joan J. Current Opinion in Structural Biology, Vol. 6, Issue 1 https://doi.org/10.1016/S0959-440X(96)80090-X	journal	February 1996
Amplification of B Cell Antigen Receptor Signaling by a Syk/ITAM Positive Feedback Loop Rolli, Véronique; Gallwitz, Maike; Wossning, Thomas Molecular Cell, Vol. 10, Issue 5 https://doi.org/10.1016/S1097-2765(02)00739-6	journal	November 2002
Structural Basis for the Inhibition of Tyrosine Kinase Activity of ZAP-70 Deindl, Sebastian; Kadlecek, Theresa A.; Brdicka, Tomas Cell, Vol. 129, Issue 4 https://doi.org/10.1016/j.cell.2007.03.039	journal	May 2007
The Src, Syk, and Tec family kinases: Distinct types of molecular switches Bradshaw, J. Michael Cellular Signalling, Vol. 22, Issue 8 https://doi.org/10.1016/j.cellsig.2010.03.001	journal	August 2010
Binding of a Diphosphorylated-ITAM peptide to spleen tyrosine kinase (Syk) induces distal conformational changes: A hydrogen exchange mass spectrometry study Catalina, M. Isabel; Fischer, Marcel J. E.; Dekker, Frank J. Journal of the American Society for Mass Spectrometry, Vol. 16, Issue 7 https://doi.org/10.1016/j.jasms.2005.02.011	journal	July 2005
Structural and Biophysical Characterization of the Syk Activation Switch Grädler, Ulrich; Schwarz, Daniel; Dresing, Verena Journal of Molecular Biology, Vol. 425, Issue 2 https://doi.org/10.1016/j.jmb.2012.11.007	journal	January 2013
Crystal Structure and NMR Studies of the Apo SH2 Domains of ZAP-70: Two Bikes Rather than a Tandem Folmer, Rutger H. A.; Geschwindner, Stefan; Xue, Yafeng Biochemistry, Vol. 41, Issue 48 https://doi.org/10.1021/bi026465e	journal	November 2002
Thermodynamic Study of the Binding of the Tandem-SH2 Domain of the Syk Kinase to a Dually Phosphorylated ITAM Peptide: Evidence for Two Conformers Grucza, Richard A.; Fütterer, Klaus; Chan, Andrew C. Biochemistry, Vol. 38, Issue 16 https://doi.org/10.1021/bi9829938	journal	March 1999
Stimulation of protein tyrosine phosphorylation by the B-lymphocyte antigen receptor Gold, Michael R.; Law, Debbie A.; DeFranco, Anthony L. Nature, Vol. 345, Issue 6278 https://doi.org/10.1038/345810a0	journal	June 1990
Molecular basis for interaction of the protein tyrosine kinase ZAP-70 with the T-cell receptor Hatada, Marcos H.; Lu, Xiaode; Laird, Ellen R. Nature, Vol. 377, Issue 6544 https://doi.org/10.1038/377032a0	journal	September 1995
T cell receptor dwell times control the kinase activity of Zap70 Klammt, Christian; Novotná, Lucie; Li, Dongyang T. Nature Immunology, Vol. 16, Issue 9 https://doi.org/10.1038/ni.3231	journal	August 2015
Origin and evolution of the adaptive immune system: genetic events and selective pressures Flajnik, Martin F.; Kasahara, Masanori Nature Reviews Genetics, Vol. 11, Issue 1 https://doi.org/10.1038/nrg2703	journal	December 2009
Insights into the allosteric regulation of Syk association with receptor ITAM, a multi-state equilibrium Feng, Chao; Post, Carol Beth Physical Chemistry Chemical Physics, Vol. 18, Issue 8 https://doi.org/10.1039/C5CP05417F	journal	January 2016
An allosteric hot spot in the tandem-SH2 domain of ZAP-70 regulates T-cell signaling Gangopadhyay, Kaustav; Manna, Bharat; Roy, Swarnendu Biochemical Journal, Vol. 477, Issue 7 https://doi.org/10.1042/BCJ20190879	journal	April 2020
Modification by covalent reaction or oxidation of cysteine residues in the tandem-SH2 domains of ZAP-70 and Syk can block phosphopeptide binding Visperas, Patrick R.; Winger, Jonathan A.; Horton, Timothy M. Biochemical Journal, Vol. 465, Issue 1 https://doi.org/10.1042/BJ20140793	journal	December 2014
Tyr130 phosphorylation triggers Syk release from antigen receptor by long-distance conformational uncoupling Zhang, Y.; Oh, H.; Burton, R. A. Proceedings of the National Academy of Sciences, Vol. 105, Issue 33 https://doi.org/10.1073/pnas.0708583105	journal	August 2008
Differential Intrinsic Enzymatic Activity of Syk and Zap-70 Protein-tyrosine Kinases Latour, Sylvain; Chow, Lionel M. L.; Veillette, Andrá Journal of Biological Chemistry, Vol. 271, Issue 37 https://doi.org/10.1074/jbc.271.37.22782	journal	September 1996
Role of the Syk autophosphorylation site and SH2 domains in B cell antigen receptor signaling. Kurosaki, T.; Johnson, S. A.; Pao, L. Journal of Experimental Medicine, Vol. 182, Issue 6 https://doi.org/10.1084/jem.182.6.1815	journal	December 1995
Database resources of the National Center for Biotechnology Information Agarwala, Richa; Barrett, Tanya; Beck, Jeff Nucleic Acids Research, Vol. 46, Issue D1 https://doi.org/10.1093/nar/gkx1095	journal	November 2017
Sequential interactions of the TCR with two distinct cytoplasmic tyrosine kinases Iwashima, M.; Irving, B.; van Oers, N. Science, Vol. 263, Issue 5150 https://doi.org/10.1126/science.7509083	journal	February 1994
Monovalent and Multivalent Ligation of the B Cell Receptor Exhibit Differential Dependence upon Syk and Src Family Kinases Mukherjee, S.; Zhu, J.; Zikherman, J. Science Signaling, Vol. 6, Issue 256 https://doi.org/10.1126/scisignal.2003220	journal	January 2013
Activation Loop Dynamics Determine the Different Catalytic Efficiencies of B Cell- and T Cell-Specific Tec Kinases Joseph, R. E.; Kleino, I.; Wales, T. E. Science Signaling, Vol. 6, Issue 290 https://doi.org/10.1126/scisignal.2004298	journal	August 2013
Structural Basis for Activation of ZAP-70 by Phosphorylation of the SH2-Kinase Linker Yan, Q.; Barros, T.; Visperas, P. R. Molecular and Cellular Biology, Vol. 33, Issue 11 https://doi.org/10.1128/MCB.01637-12	journal	March 2013
T Cell-Dependent B Cell Activation Parker, D. C. Annual Review of Immunology, Vol. 11, Issue 1 https://doi.org/10.1146/annurev.iy.11.040193.001555	journal	April 1993
An electrostatic selection mechanism controls sequential kinase signaling downstream of the T cell receptor Shah, Neel H.; Wang, Qi; Yan, Qingrong eLife, Vol. 5 https://doi.org/10.7554/eLife.20105	journal	October 2016

Similar Records

Chromosomal location of the Syk and ZAP-70 tyrosine kinase genes in mice and humans

Journal Article · Fri Dec 30 23:00:00 EST 1994 · Immunogenetics · OSTI ID:68498

Selective Targeting of SH2 Domain–Phosphotyrosine Interactions of Src Family Tyrosine Kinases with Monobodies

Journal Article · Mon May 01 00:00:00 EDT 2017 · Journal of Molecular Biology · OSTI ID:1368269

Autoinhibition of Bruton's tyrosine kinase (Btk) and activation by soluble inositol hexakisphosphate

Journal Article · Thu Feb 19 23:00:00 EST 2015 · eLife · OSTI ID:1628833

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
Biochemistry & Molecular Biology
conformational landscape
evolution
hydrogen-deuterium exchange mass spectrometry
protein dynamics
tyrosine kinase signaling

Differences in the dynamics of the tandem-SH2 modules of the Syk and ZAP-70 tyrosine kinases

Citation Formats

References (32)

Similar Records

Related Subjects