Format

Send to

Choose Destination
Science. 2015 Oct 23;350(6259):aac5137. doi: 10.1126/science.aac5137.

HIV-1 Nef hijacks clathrin coats by stabilizing AP-1:Arf1 polygons.

Author information

1
Department of Molecular and Cell Biology and California Institute for Quantitative Biosciences, University of California, Berkeley, Berkeley, CA 94720, USA.
2
Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
3
Department of Molecular and Cell Biology and California Institute for Quantitative Biosciences, University of California, Berkeley, Berkeley, CA 94720, USA. Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA. jimhurley@berkeley.edu.

Abstract

The lentiviruses HIV and simian immunodeficiency virus (SIV) subvert intracellular membrane traffic as part of their replication cycle. The lentiviral Nef protein helps viruses evade innate and adaptive immune defenses by hijacking the adaptor protein 1 (AP-1) and AP-2 clathrin adaptors. We found that HIV-1 Nef and the guanosine triphosphatase Arf1 induced trimerization and activation of AP-1. Here we report the cryo-electron microscopy structures of the Nef- and Arf1-bound AP-1 trimer in the active and inactive states. A central nucleus of three Arf1 molecules organizes the trimers. We combined the open trimer with a known dimer structure and thus predicted a hexagonal assembly with inner and outer faces that bind the membranes and clathrin, respectively. Hexagons were directly visualized and the model validated by reconstituting clathrin cage assembly. Arf1 and Nef thus play interconnected roles in allosteric activation, cargo recruitment, and coat assembly, revealing an unexpectedly intricate organization of the inner AP-1 layer of the clathrin coat.

PMID:
26494761
PMCID:
PMC4638387
DOI:
10.1126/science.aac5137
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center