A1 Journal article (refereed)
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 (2022)


Tossavainen, H., Uğurlu, H., Karjalainen, M., Hellman, M., Antenucci, L., Fagerlund, R., Saksela, K., & Permi, P. (2022). 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. Structure, 30(6), 828-839.e6. https://doi.org/10.1016/j.str.2022.03.006


JYU authors or editors


Publication details

All authors or editors: Tossavainen, Helena; Uğurlu, Hasan; Karjalainen, Mikael; Hellman, Maarit; Antenucci, Lina; Fagerlund, Riku; Saksela, Kalle; Permi, Perttu

Journal or series: Structure

ISSN: 0969-2126

eISSN: 1878-4186

Publication year: 2022

Publication date: 06/04/2022

Volume: 30

Issue number: 6

Pages range: 828-839.e6

Publisher: Elsevier

Publication country: Netherlands

Publication language: English

DOI: https://doi.org/10.1016/j.str.2022.03.006

Publication open access: Openly available

Publication channel open access: Partially open access channel

Publication is parallel published (JYX): https://jyx.jyu.fi/handle/123456789/80830


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.


Keywords: proteins; cell signaling; viruses; alphaviruses; retroviruses

Free keywords: EEEV nsP3; HTLV-1 Gag; isothermal titration calorimetry; SH3; SNX9; solution NMR spectroscopy


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Ministry reporting: Yes

Reporting Year: 2022

Preliminary JUFO rating: 2


Last updated on 2022-14-09 at 11:57