Structure of SNX9 SH3 in complex with a viral ligand reveals the molecular basis of its unique specificity for alanine-containing class I SH3 motifs.

Alanine Animals Binding Sites Horses Ligands Peptides / chemistry Protein Binding src Homology Domains
EEEV nsP3 HTLV-1 Gag SH3 SNX9 isothermal titration calorimetry solution NMR spectroscopy

Journal

Structure (London, England : 1993)
ISSN: 1878-4186
Titre abrégé: Structure
Pays: United States
ID NLM: 101087697

Informations de publication

Date de publication:
02 06 2022
Historique:
received: 12 08 2021
revised: 22 12 2021
accepted: 04 03 2022
pubmed: 8 4 2022
medline: 9 6 2022
entrez: 7 4 2022
Statut: ppublish

Résumé

Class I SH3 domain-binding motifs generally comply with the consensus sequence [R/K]xØPxxP, the hydrophobic residue Ø being proline or leucine. We have studied the unusual Ø = Ala-specificity of SNX9 SH3 by determining its complex structure with a peptide present in eastern equine encephalitis virus (EEEV) nsP3. The structure revealed the length and composition of the n-Src loop as important factors determining specificity. We also compared the affinities of EEEV nsP3 peptide, its mutants, and cellular ligands to SNX9 SH3. These data suggest that nsP3 has evolved to minimize reduction of conformational entropy upon binding, hence acquiring stronger affinity, enabling takeover of SNX9. The RxAPxxP motif was also found in human T cell leukemia virus-1 (HTLV-1) Gag polyprotein. We found that this motif was required for efficient HTLV-1 infection, and that the specificity of SNX9 SH3 for the RxAPxxP core binding motif was importantly involved in this process.

Identifiants

DOI: 10.1016/j.str.2022.03.006 PMID: 35390274
pubmed: 35390274
pii: S0969-2126(22)00087-9
doi: 10.1016/j.str.2022.03.006
pii:
doi:

Substances chimiques

Ligands 0
Peptides 0
Alanine OF5P57N2ZX

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

828-839.e6

Informations de copyright

Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests The authors declare no competing interests.

Auteurs

Helena Tossavainen (H)

Department of Biological and Environmental Science, University of Jyvaskyla, Jyvaskyla FI-40014, Finland.

Hasan Uğurlu (H)

Department of Virology, University of Helsinki and Helsinki University Hospital, Helsinki FI-00014 Finland.

Mikael Karjalainen (M)

Department of Chemistry, Nanoscience Center, University of Jyvaskyla, Jyvaskyla FI-40014, Finland.

Maarit Hellman (M)

Department of Chemistry, Nanoscience Center, University of Jyvaskyla, Jyvaskyla FI-40014, Finland.

Lina Antenucci (L)

Department of Biological and Environmental Science, University of Jyvaskyla, Jyvaskyla FI-40014, Finland; Department of Chemistry, Nanoscience Center, University of Jyvaskyla, Jyvaskyla FI-40014, Finland.

Riku Fagerlund (R)

Department of Virology, University of Helsinki and Helsinki University Hospital, Helsinki FI-00014 Finland.

Kalle Saksela (K)

Department of Virology, University of Helsinki and Helsinki University Hospital, Helsinki FI-00014 Finland.

Perttu Permi (P)

Department of Biological and Environmental Science, University of Jyvaskyla, Jyvaskyla FI-40014, Finland; Department of Chemistry, Nanoscience Center, University of Jyvaskyla, Jyvaskyla FI-40014, Finland. Electronic address: perttu.permi@jyu.fi.

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Classifications MeSH

questionsmedicales.fr › Acides aminés, peptides et protéines › Acides aminés › Alanine › Structure of SNX9 SH3 in complex with a viral...
questionsmedicales.fr › Eucaryotes › Animaux › Structure of SNX9 SH3 in complex with a viral...
questionsmedicales.fr › Phénomènes chimiques › Phénomènes biochimiques › Sites de fixation › Structure of SNX9 SH3 in complex with a viral...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Perissodactyla › Equidae › Equus caballus › Structure of SNX9 SH3 in complex with a viral...
questionsmedicales.fr › Actions chimiques et utilisations › Utilisations spécialisées de produits chimiques › Produits chimiques de laboratoire › Ligands › Structure of SNX9 SH3 in complex with a viral...
questionsmedicales.fr › Acides aminés, peptides et protéines › Peptides › Structure of SNX9 SH3 in complex with a viral...
questionsmedicales.fr › Métabolisme › Liaison aux protéines › Structure of SNX9 SH3 in complex with a viral...
questionsmedicales.fr › Phénomènes chimiques › Phénomènes biochimiques › Conformation moléculaire › Conformation des protéines › Éléments structuraux des protéines › Motifs et domaines d'intéraction protéique › Domaine d'homologie SRC › Structure of SNX9 SH3 in complex with a viral...