undefined

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

Year of publication

2022

Authors

Tossavainen, Helena; Ugurlu, Hasan; Karjalainen, Mikael; Hellman, Maarit; Antenucci, Lina; Fagerlund, Riku; Saksela, Kalle; Permi, Perttu

Abstract

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.
Show more

Organizations and authors

University of Jyväskylä

Tossavainen Helena Orcid -palvelun logo

Antenucci Lina Orcid -palvelun logo

Hellman Maarit

Karjalainen Mikael Orcid -palvelun logo

Permi Perttu Orcid -palvelun logo

University of Helsinki

Ugurlu Hasan

Saksela Kalle

Fagerlund Riku

Helsinki University Hospital Catchment Area

Ugurlu Hasan

Saksela Kalle

Fagerlund Riku

Publication type

Publication format

Article

Parent publication type

Journal

Article type

Original article

Audience

Scientific

Peer-reviewed

Peer-Reviewed

MINEDU's publication type classification code

A1 Journal article (refereed), original research

Publication channel information

Parent publication name

Structure

Volume

30

Issue

6

Pages

828-+

​Publication forum

67657

​Publication forum level

2

Open access

Open access in the publisher’s service

Yes

Open access of publication channel

Partially open publication channel

License of the publisher’s version

CC BY

Self-archived

Yes

License of the self-archived publication

CC BY

Other information

Fields of science

Biochemistry, cell and molecular biology; Plant biology, microbiology, virology; Biomedicine

Keywords

[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]

Publication country

United States

Internationality of the publisher

International

Language

English

International co-publication

No

Co-publication with a company

No

DOI

10.1016/j.str.2022.03.006

The publication is included in the Ministry of Education and Culture’s Publication data collection

Yes