A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä
Evolutionary plasticity of SH3 domain binding by Nef proteins of the HIV-1/SIVcpz lentiviral lineage (2021)
Zhao, Z., Fagerlund, R., Tossavainen, H., Hopfensperger, K., Lotke, R., Srinivasachar, B. S., Kirchhoff, F., Permi, P., Sato, K., Sauter, D., & Saksela, K. (2021). Evolutionary plasticity of SH3 domain binding by Nef proteins of the HIV-1/SIVcpz lentiviral lineage. PLoS Pathogens, 17(11), Article e1009728. https://doi.org/10.1371/journal.ppat.1009728
JYU-tekijät tai -toimittajat
Julkaisun tiedot
Julkaisun kaikki tekijät tai toimittajat: Zhao, Zhe; Fagerlund, Riku; Tossavainen, Helena; Hopfensperger, Kristina; Lotke, Rishikesh; Srinivasachar, Badarinarayan Smitha; Kirchhoff, Frank; Permi, Perttu; Sato, Kei; Sauter, Daniel; et al.
Lehti tai sarja: PLoS Pathogens
ISSN: 1553-7366
eISSN: 1553-7374
Julkaisuvuosi: 2021
Ilmestymispäivä: 15.11.2021
Volyymi: 17
Lehden numero: 11
Artikkelinumero: e1009728
Kustantaja: Public Library of Science
Julkaisumaa: Yhdysvallat (USA)
Julkaisun kieli: englanti
DOI: https://doi.org/10.1371/journal.ppat.1009728
Julkaisun avoin saatavuus: Avoimesti saatavilla
Julkaisukanavan avoin saatavuus: Kokonaan avoin julkaisukanava
Julkaisu on rinnakkaistallennettu (JYX): https://jyx.jyu.fi/handle/123456789/78967
Tiivistelmä
The accessory protein Nef of human and simian immunodeficiency viruses (HIV and SIV) is an important pathogenicity factor known to interact with cellular protein kinases and other signaling proteins. A canonical SH3 domain binding motif in Nef is required for most of these interactions. For example, HIV-1 Nef activates the tyrosine kinase Hck by tightly binding to its SH3 domain. An archetypal contact between a negatively charged SH3 residue and a highly conserved arginine in Nef (Arg77) plays a key role here. Combining structural analyses with functional assays, we here show that Nef proteins have also developed a distinct structural strategy—termed the "R-clamp”—that favors the formation of this salt bridge via buttressing Arg77. Comparison of evolutionarily diverse Nef proteins revealed that several distinct R-clamps have evolved that are functionally equivalent but differ in the side chain compositions of Nef residues 83 and 120. Whereas a similar R-clamp design is shared by Nef proteins of HIV-1 groups M, O, and P, as well as SIVgor, the Nef proteins of SIV from the Eastern chimpanzee subspecies (SIVcpzP.t.s.) exclusively utilize another type of R-clamp. By contrast, SIV of Central chimpanzees (SIVcpzP.t.t.) and HIV-1 group N strains show more heterogenous R-clamp design principles, including a non-functional evolutionary intermediate of the aforementioned two classes. These data add to our understanding of the structural basis of SH3 binding and kinase deregulation by Nef, and provide an interesting example of primate lentiviral protein evolution.
YSO-asiasanat: proteiinit; kinaasit; virukset; HIV-tartunta; evoluutio
Liittyvät organisaatiot
Hankkeet, joissa julkaisu on tehty
- Peptidoglykaanihydrolaasit vastaan antibioottiresistentti Staphylococcus aureus
- Permi, Perttu
- Suomen Akatemia
- Peptidoglyg. vastaan resistentti Staphylococcus aureus
- Permi, Perttu
- Jane ja Aatos Erkon säätiö
OKM-raportointi: Kyllä
Raportointivuosi: 2021
JUFO-taso: 2