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 moreOrganizations and authors
University of Jyväskylä
Hellman Maarit
Publication type
Publication format
Article
Parent publication type
Journal
Article type
Original article
Audience
ScientificPeer-reviewed
Peer-ReviewedMINEDU's publication type classification code
A1 Journal article (refereed), original researchPublication channel information
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