PMID- 21483490
OWN - NLM
STAT- MEDLINE
DCOM- 20111212
LR  - 20220129
IS  - 1553-7374 (Electronic)
IS  - 1553-7366 (Print)
IS  - 1553-7366 (Linking)
VI  - 7
IP  - 3
DP  - 2011 Mar
TI  - Novel escape mutants suggest an extensive TRIM5alpha binding site spanning the entire 
      outer surface of the murine leukemia virus capsid protein.
PG  - e1002011
LID - 10.1371/journal.ppat.1002011 [doi]
LID - e1002011
AB  - After entry into target cells, retroviruses encounter the host restriction 
      factors such as Fv1 and TRIM5alpha. 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 TRIM5alpha 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 TRIM5alpha (rhTRIM5alpha)-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 beta-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 
      TRIM5alpha, indicating significant differences in the binding interaction between 
      N-MLV and the two TRIM5alphas, 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 TRIM5alpha binding.
FAU - Ohkura, Sadayuki
AU  - Ohkura S
AD  - Division of Virology, MRC National Institute for Medical Research, London, United 
      Kingdom.
FAU - Goldstone, David C
AU  - Goldstone DC
FAU - Yap, Melvyn W
AU  - Yap MW
FAU - Holden-Dye, Kate
AU  - Holden-Dye K
FAU - Taylor, Ian A
AU  - Taylor IA
FAU - Stoye, Jonathan P
AU  - Stoye JP
LA  - eng
SI  - PDB/2Y4Z
GR  - MC_U117512710/MRC_/Medical Research Council/United Kingdom
GR  - MC_U117565647/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
DEP - 20110331
PL  - United States
TA  - PLoS Pathog
JT  - PLoS pathogens
JID - 101238921
RN  - 0 (Antiviral Restriction Factors)
RN  - 0 (Capsid Proteins)
RN  - 0 (Carrier Proteins)
RN  - 0 (Tripartite Motif Proteins)
RN  - EC 2.3.2.27 (TRIM5 protein, human)
RN  - EC 2.3.2.27 (Ubiquitin-Protein Ligases)
SB  - IM
MH  - Animals
MH  - Antiviral Restriction Factors
MH  - Base Sequence
MH  - Binding Sites
MH  - Capsid/*metabolism
MH  - Capsid Proteins/genetics/*metabolism
MH  - Carrier Proteins/*metabolism
MH  - Cell Line
MH  - Humans
MH  - Leukemia Virus, Murine/genetics/*metabolism
MH  - Macaca mulatta
MH  - Mice
MH  - Mutation
MH  - Protein Interaction Domains and Motifs
MH  - Sequence Analysis, DNA
MH  - Tripartite Motif Proteins
MH  - Ubiquitin-Protein Ligases
PMC - PMC3068999
COIS- The authors have declared that no competing interests exist.
EDAT- 2011/04/13 06:00
MHDA- 2011/12/14 06:00
PMCR- 2011/03/31
CRDT- 2011/04/13 06:00
PHST- 2010/11/05 00:00 [received]
PHST- 2011/01/28 00:00 [accepted]
PHST- 2011/04/13 06:00 [entrez]
PHST- 2011/04/13 06:00 [pubmed]
PHST- 2011/12/14 06:00 [medline]
PHST- 2011/03/31 00:00 [pmc-release]
AID - PPATHOGENS-D-10-00275 [pii]
AID - 10.1371/journal.ppat.1002011 [doi]
PST - ppublish
SO  - PLoS Pathog. 2011 Mar;7(3):e1002011. doi: 10.1371/journal.ppat.1002011. Epub 2011 
      Mar 31.