Details
| Original language | English |
|---|---|
| Article number | 100026 |
| Number of pages | 9 |
| Journal | Journal of Structural Biology: X |
| Volume | 4 |
| Early online date | 27 May 2020 |
| Publication status | Published - 2020 |
Abstract
Phosphotyrosine (pY) signaling is instrumental to numerous cellular processes. pY recognition occurs through specialized protein modules, among which the Src-homology 2 (SH2) domain is the most common. SH2 domains are small protein modules with an invariant fold, and are present in more than a hundred proteins with different function. Here we ask the question of how such a structurally conserved, small protein domain can recognize distinct phosphopeptides with the breath of binding affinity, specificity and kinetic parameters necessary for proper control of pY-dependent signaling and rapid cellular response. We review the current knowledge on structure, thermodynamics and kinetics of SH2–phosphopeptide complexes and conclude that selective phosphopeptide recognition is governed by both structure and dynamics of the SH2 domain, as well as by the kinetics of the binding events. Further studies on the thermodynamic and kinetic properties of SH2–phosphopeptide complexes, beyond their structure, are required to understand signaling regulation.
Keywords
- Binding specificity, Phosphotyrosine, pY signalling, SH2 domain
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Structural Biology
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In: Journal of Structural Biology: X, Vol. 4, 100026, 2020.
Research output: Contribution to journal › Article › Research › peer review
}
TY - JOUR
T1 - Specificity and regulation of phosphotyrosine signaling through SH2 domains
AU - Marasco, Michelangelo
AU - Carlomagno, Teresa
N1 - Funding Information: M.M. was supported by a fellowship from the Hannover School for Biomolecular Drug Research and was a member of the Hannover Biomedical Research School (HBRS) and the MD/PhD program “Molecular Medicine”. T.C received funding from the German Research Council (DFG, grant #: CA294/20-1 ).
PY - 2020
Y1 - 2020
N2 - Phosphotyrosine (pY) signaling is instrumental to numerous cellular processes. pY recognition occurs through specialized protein modules, among which the Src-homology 2 (SH2) domain is the most common. SH2 domains are small protein modules with an invariant fold, and are present in more than a hundred proteins with different function. Here we ask the question of how such a structurally conserved, small protein domain can recognize distinct phosphopeptides with the breath of binding affinity, specificity and kinetic parameters necessary for proper control of pY-dependent signaling and rapid cellular response. We review the current knowledge on structure, thermodynamics and kinetics of SH2–phosphopeptide complexes and conclude that selective phosphopeptide recognition is governed by both structure and dynamics of the SH2 domain, as well as by the kinetics of the binding events. Further studies on the thermodynamic and kinetic properties of SH2–phosphopeptide complexes, beyond their structure, are required to understand signaling regulation.
AB - Phosphotyrosine (pY) signaling is instrumental to numerous cellular processes. pY recognition occurs through specialized protein modules, among which the Src-homology 2 (SH2) domain is the most common. SH2 domains are small protein modules with an invariant fold, and are present in more than a hundred proteins with different function. Here we ask the question of how such a structurally conserved, small protein domain can recognize distinct phosphopeptides with the breath of binding affinity, specificity and kinetic parameters necessary for proper control of pY-dependent signaling and rapid cellular response. We review the current knowledge on structure, thermodynamics and kinetics of SH2–phosphopeptide complexes and conclude that selective phosphopeptide recognition is governed by both structure and dynamics of the SH2 domain, as well as by the kinetics of the binding events. Further studies on the thermodynamic and kinetic properties of SH2–phosphopeptide complexes, beyond their structure, are required to understand signaling regulation.
KW - Binding specificity
KW - Phosphotyrosine
KW - pY signalling
KW - SH2 domain
UR - http://www.scopus.com/inward/record.url?scp=85085930804&partnerID=8YFLogxK
U2 - 10.1016/j.yjsbx.2020.100026
DO - 10.1016/j.yjsbx.2020.100026
M3 - Article
AN - SCOPUS:85085930804
VL - 4
JO - Journal of Structural Biology: X
JF - Journal of Structural Biology: X
M1 - 100026
ER -