PDBsum entry 2y4z

Viral protein

PDB id: 2y4z

Contents

Protein chain

135 a.a.

Ligands

GOL

Waters ×99

PDB id:

2y4z

Name:

Viral protein

Title:

Structure of the amino-terminal capsid restriction escape mutation n- mlv l10w

Structure:

Capsid protein p30. Chain: a. Fragment: n-terminal domain, residues 215-346. Synonym: ca. Engineered: yes. Mutation: yes

Source:

Murine leukemia virus. Organism_taxid: 11786. Expressed in: escherichia coli. Expression_system_taxid: 469008.

Resolution:

2.00Å R-factor: 0.177 R-free: 0.244

Authors:

D.C.Goldstone,K.Holden-Dye,S.Ohkura,J.P.Stoye,I.A.Taylor

Key ref:

S.Ohkura et al. (2011). Novel escape mutants suggest an extensive TRIM5α binding site spanning the entire outer surface of the murine leukemia virus capsid protein. Plos Pathog, 7, e1002011. PubMed id: 21483490

Date:

11-Jan-11 Release date: 23-Nov-11

Protein chain

P03336  (GAG_MLVAV) -  Gag polyprotein from AKV murine leukemia virus

Seq: 537 a.a.

Struc: 135 a.a.*

* PDB and UniProt seqs differ at 4 residue positions (black crosses)

Plos Pathog 7:e1002011 (2011)

PubMed id: 21483490

Novel escape mutants suggest an extensive TRIM5α binding site spanning the entire outer surface of the murine leukemia virus capsid protein.

S.Ohkura, D.C.Goldstone, M.W.Yap, K.Holden-Dye, I.A.Taylor, J.P.Stoye.

ABSTRACT

After entry into target cells, retroviruses encounter the host restriction factors such as Fv1 and TRIM5α. While it is clear that these factors target retrovirus capsid proteins (CA), recognition remains poorly defined in the absence of structural information. To better understand the binding interaction between TRIM5α and CA, we selected a panel of novel N-tropic murine leukaemia virus (N-MLV) escape mutants by a serial passage of replication competent N-MLV in rhesus macaque TRIM5α (rhTRIM5α)-positive cells using a small percentage of unrestricted cells to allow multiple rounds of virus replication. The newly identified mutations, many of which involve changes in charge, are distributed over the outer 'top' surface of N-MLV CA, including the N-terminal β-hairpin, and map up to 29 A(o) apart. Biological characterisation with a number of restriction factors revealed that only one of the new mutations affects restriction by human TRIM5α, indicating significant differences in the binding interaction between N-MLV and the two TRIM5αs, whereas three of the mutations result in dual sensitivity to Fv1(n) and Fv1(b). Structural studies of two mutants show that no major changes in the overall CA conformation are associated with escape from restriction. We conclude that interactions involving much, if not all, of the surface of CA are vital for TRIM5α binding.