EMD-24698

Single-particle
4.4 Å
EMD-24698 Deposition: 16/08/2021
Map released: 24/08/2022
Last modified: 06/09/2023
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-24698

Cryo-EM structure of the HIV-1 restriction factor human SERINC3

EMD-24698

Single-particle
4.4 Å
EMD-24698 Deposition: 16/08/2021
Map released: 24/08/2022
Last modified: 06/09/2023
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Homo sapiens, synthetic construct
Sample: hSERINC3-SiA
Fitted models: 7ru6 (Avg. Q-score: 0.323)

Deposition Authors: Purdy MD , Leonhardt SA , Yeager M
Antiviral HIV-1 SERINC restriction factors disrupt virus membrane asymmetry.
PUBMED: 37474505
DOI: doi:10.1038/s41467-023-39262-2
ISSN: 2041-1723
Abstract:
The host proteins SERINC3 and SERINC5 are HIV-1 restriction factors that reduce infectivity when incorporated into the viral envelope. The HIV-1 accessory protein Nef abrogates incorporation of SERINCs via binding to intracellular loop 4 (ICL4). Here, we determine cryoEM maps of full-length human SERINC3 and an ICL4 deletion construct, which reveal that hSERINC3 is comprised of two α-helical bundles connected by a ~ 40-residue, highly tilted, "crossmember" helix. The design resembles non-ATP-dependent lipid transporters. Consistently, purified hSERINCs reconstituted into proteoliposomes induce flipping of phosphatidylserine (PS), phosphatidylethanolamine and phosphatidylcholine. Furthermore, SERINC3, SERINC5 and the scramblase TMEM16F expose PS on the surface of HIV-1 and reduce infectivity, with similar results in MLV. SERINC effects in HIV-1 and MLV are counteracted by Nef and GlycoGag, respectively. Our results demonstrate that SERINCs are membrane transporters that flip lipids, resulting in a loss of membrane asymmetry that is strongly correlated with changes in Env conformation and loss of infectivity.