Revealing Allostery in PTPN11 SH2 Domains from MD Simulations.

Allosteric regulation Molecular dynamics simulations Phosphatases Principal component analysis Protein dynamics Protein function SH2 domains

Journal

Methods in molecular biology (Clifton, N.J.)
ISSN: 1940-6029
Titre abrégé: Methods Mol Biol
Pays: United States
ID NLM: 9214969

Informations de publication

Date de publication:
2023
Historique:
medline: 6 9 2023
pubmed: 5 9 2023
entrez: 5 9 2023
Statut: ppublish

Résumé

Src-homology 2 (SH2) domains are protein interaction domains that bind to specific peptide motifs containing phosphotyrosine. SHP2, a tyrosine phosphatase encoded by PTPN11 gene, which has been emerged as positive or negative modulator in multiple signaling pathways, contains two SH2 domains, respectively, called N-SH2 and C-SH2. These domains play a relevant role in regulating SHP2 activity, either by recognizing its binding partners or by blocking its catalytic site. Considering the multiple functions that these domains carry out in SHP2, N-SH2 and C-SH2 represent an interesting case of study. In this chapter, we present a methodology that permits, by means of the principal component analysis (PCA), to study and to rationalize the structures adopted by the SH2 domains, in terms of the conformations of their binding sites. The structures can be distinguished, grouped, classified, and reported in a diagram. This approach permits to identify the accessible conformations of the SH2 domains in different binding conditions and to eventually reveal allosteric interactions. The method further reveals that the conformation dynamics of N-SH2 and C-SH2 strongly differ, which likely reflects their distinct functional roles.

Identifiants

pubmed: 37668969
doi: 10.1007/978-1-0716-3393-9_4
doi:

Substances chimiques

Phosphotyrosine 21820-51-9

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

59-75

Informations de copyright

© 2023. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.

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Auteurs

Massimiliano Anselmi (M)

Theoretical Physics and Center for Biophysics, Saarland University, Saarbrücken, Germany. massimiliano.anselmi@uni-saarland.de.

Jochen S Hub (JS)

Theoretical Physics and Center for Biophysics, Saarland University, Saarbrücken, Germany.

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