7tbp

From Proteopedia

X-ray structure of the HIV-1 myristoylated matrix protein

Structural highlights

7tbp is a 3 chain structure with sequence from Human immunodeficiency virus 1. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.151Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

GAG_HV1N5 Matrix protein p17 targets Gag and Gag-Pol polyproteins to the plasma membrane via a multipartite membrane binding signal, that includes its myristoylated N-terminus. Also mediates nuclear localization of the preintegration complex. Implicated in the release from host cell mediated by Vpu. Capsid protein p24 forms the conical core of the virus that encapsulates the genomic RNA-nucleocapsid complex. Nucleocapsid protein p7 encapsulates and protects viral dimeric unspliced (genomic) RNA. Binds these RNAs through its zinc fingers. p6-gag plays a role in budding of the assembled particle by interacting with the host class E VPS proteins TSG101 and PDCD6IP/AIP1 (By similarity).

Publication Abstract from PubMed

During the late phase of HIV type 1 (HIV-1) infection cycle, the virally encoded Gag polyproteins are targeted to the inner leaflet of the plasma membrane (PM) for assembly, formation of immature particles, and virus release. Gag binding to the PM is mediated by interactions of the N-terminally myristoylated matrix (myrMA) domain with phosphatidylinositol 4,5-bisphosphate. Formation of a myrMA lattice on the PM is an obligatory step for the assembly of immature HIV-1 particles and envelope (Env) incorporation. Atomic details of the myrMA lattice and how it mediates Env incorporation are lacking. Herein, we present the X-ray structure of myrMA at 2.15 A. The myrMA lattice is arranged as a hexamer of trimers with a central hole, thought to accommodate the C-terminal tail of Env to promote incorporation into virions. The trimer-trimer interactions in the lattice are mediated by the N-terminal loop of one myrMA molecule and alpha-helices I-II, as well as the 310 helix of a myrMA molecule from an adjacent trimer. We provide evidence that substitution of MA residues Leu13 and Leu31, previously shown to have adverse effects on Env incorporation, induced a conformational change in myrMA, which may destabilize the trimer-trimer interactions within the lattice. We also show that PI(4,5)P2 is capable of binding to alternating sites on MA, consistent with an MA-membrane binding mechanism during assembly of the immature particle and upon maturation. Altogether, these findings advance our understanding of a key mechanism in HIV-1 particle assembly.

Atomic view of the HIV-1 matrix lattice; implications on virus assembly and envelope incorporation.,Samal AB, Green TJ, Saad JS Proc Natl Acad Sci U S A. 2022 Jun 7;119(23):e2200794119. doi: , 10.1073/pnas.2200794119. Epub 2022 Jun 3. PMID:35658080^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Samal AB, Green TJ, Saad JS. Atomic view of the HIV-1 matrix lattice; implications on virus assembly and envelope incorporation. Proc Natl Acad Sci U S A. 2022 Jun 7;119(23):e2200794119. PMID:35658080 doi:10.1073/pnas.2200794119