2H3I

Solution structure of the HIV-1 myristoylated Matrix protein

PDB DOI: https://doi.org/10.2210/pdb2H3I/pdb

Classification: VIRAL PROTEIN
Organism(s): Human immunodeficiency virus 1
Expression System: Escherichia coli
Mutation(s): No

Deposited: 2006-05-22 Released: 2006-07-25
Deposition Author(s): Saad, J.S., Miller, J., Tai, J., Kim, A., Ghanam, R.H., Summers, M.F.

Experimental Data Snapshot

Method: SOLUTION NMR
Conformers Calculated: 50
Conformers Submitted: 20
Selection Criteria: target function

wwPDB Validation 3D Report Full Report

This is version 1.3 of the entry. See complete history.

Literature

Structural basis for targeting HIV-1 Gag proteins to the plasma membrane for virus assembly.

Saad, J.S., Miller, J., Tai, J., Kim, A., Ghanam, R.H., Summers, M.F.

(2006) Proc Natl Acad Sci U S A 103: 11364-11369

PubMed: 16840558 Search on PubMedSearch on PubMed Central
DOI: https://doi.org/10.1073/pnas.0602818103
Primary Citation of Related Structures:
2H3F, 2H3I, 2H3Q, 2H3V, 2H3Z

PubMed Abstract:
During the late phase of HIV type 1 (HIV-1) replication, newly synthesized retroviral Gag proteins are targeted to the plasma membrane of most hematopoietic cell types, where they colocalize at lipid rafts and assemble into immature virions. Membrane binding is mediated by the matrix (MA) domain of Gag, a 132-residue polypeptide containing an N-terminal myristyl group that can adopt sequestered and exposed conformations. Although exposure is known to promote membrane binding, the mechanism by which Gag is targeted to specific membranes has yet to be established. Recent studies have shown that phosphatidylinositol (PI) 4,5-bisphosphate [PI(4,5)P(2)], a factor that regulates localization of cellular proteins to the plasma membrane, also regulates Gag localization and assembly. Here we show that PI(4,5)P(2) binds directly to HIV-1 MA, inducing a conformational change that triggers myristate exposure. Related phosphatidylinositides PI, PI(3)P, PI(4)P, PI(5)P, and PI(3,5)P(2) do not bind MA with significant affinity or trigger myristate exposure. Structural studies reveal that PI(4,5)P(2) adopts an "extended lipid" conformation, in which the inositol head group and 2'-fatty acid chain bind to a hydrophobic cleft, and the 1'-fatty acid and exposed myristyl group bracket a conserved basic surface patch previously implicated in membrane binding. Our findings indicate that PI(4,5)P(2) acts as both a trigger of the myristyl switch and a membrane anchor and suggest a potential mechanism for targeting Gag to membrane rafts.

Organizational Affiliation

Howard Hughes Medical Institute, University of Maryland, Baltimore County, 1000 Hilltop Circle, Baltimore, MD 21250, USA.

Macromolecule Content

Total Structure Weight: 14.96 kDa
Atom Count: 1,049
Modelled Residue Count: 131
Deposited Residue Count: 131
Unique protein chains: 1

Macromolecules

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
Gag polyprotein	A	131	Human immunodeficiency virus 1	Mutation(s): 0
UniProt
Find proteins for P12497 (Human immunodeficiency virus type 1 group M subtype B (isolate NY5)) Explore P12497 Go to UniProtKB: P12497
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P12497
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 1 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
MYR Query on MYR Download Ideal Coordinates CCD File SDF format, chain B [auth A] MOL2 format, chain B [auth A]	B [auth A]	MYRISTIC ACID C₁₄ H₂₈ O₂ TUNFSRHWOTWDNC-UHFFFAOYSA-N		Interactions Focus chain B [auth A]