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TitleA bipartite structural organization defines the SERINC family of HIV-1 restriction factors.
Journal, issue, pagesNat Struct Mol Biol, Vol. 27, Issue 1, Page 78-83, Year 2020
Publish dateJan 6, 2020
AuthorsValerie E Pye / Annachiara Rosa / Cinzia Bertelli / Weston B Struwe / Sarah L Maslen / Robin Corey / Idlir Liko / Mark Hassall / Giada Mattiuzzo / Allison Ballandras-Colas / Andrea Nans / Yasuhiro Takeuchi / Phillip J Stansfeld / J Mark Skehel / Carol V Robinson / Massimo Pizzato / Peter Cherepanov /
PubMed AbstractThe human integral membrane protein SERINC5 potently restricts HIV-1 infectivity and sensitizes the virus to antibody-mediated neutralization. Here, using cryo-EM, we determine the structures of ...The human integral membrane protein SERINC5 potently restricts HIV-1 infectivity and sensitizes the virus to antibody-mediated neutralization. Here, using cryo-EM, we determine the structures of human SERINC5 and its orthologue from Drosophila melanogaster at subnanometer and near-atomic resolution, respectively. The structures reveal a novel fold comprised of ten transmembrane helices organized into two subdomains and bisected by a long diagonal helix. A lipid binding groove and clusters of conserved residues highlight potential functional sites. A structure-based mutagenesis scan identified surface-exposed regions and the interface between the subdomains of SERINC5 as critical for HIV-1-restriction activity. The same regions are also important for viral sensitization to neutralizing antibodies, directly linking the antiviral activity of SERINC5 with remodeling of the HIV-1 envelope glycoprotein.
External linksNat Struct Mol Biol / PubMed:31907454 / PubMed Central
MethodsEM (single particle)
Resolution3.33 - 8.2 Å
Structure data

EMDB-10277:
Cryo-EM structure of human SERINC5 in LMNG micelles, bound to Fab.
Method: EM (single particle) / Resolution: 8.2 Å

10279

6sp2

EMDB-10279, PDB-6sp2:
CryoEM structure of SERINC from Drosophila melanogaster
Method: EM (single particle) / Resolution: 3.33 Å

Chemicals

ChemComp-LMN:
Lauryl Maltose Neopentyl Glycol / detergent*YM

ChemComp-P5S:
O-[(R)-{[(2R)-2,3-bis(octadecanoyloxy)propyl]oxy}(hydroxy)phosphoryl]-L-serine / Phosphatidylserine

ChemComp-CDL:
CARDIOLIPIN / phospholipid*YM / Cardiolipin

Source
  • Homo sapiens (human)
  • Mus musculus (house mouse)
  • drosophila melanogaster (fruit fly)
KeywordsMEMBRANE PROTEIN / Anti-retroviral / TM10 / SERINC fold / novel fold

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