 |
PDBsum entry 2y4z
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Viral protein
|
PDB id
|
|
|
|
2y4z
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
Novel escape mutants suggest an extensive trim5α binding site spanning the entire outer surface of the murine leukemia virus capsid protein.
|
|
|
Authors
|
|
S.Ohkura,
D.C.Goldstone,
M.W.Yap,
K.Holden-Dye,
I.A.Taylor,
J.P.Stoye.
|
|
|
Ref.
|
|
Plos Pathog, 2011,
7,
e1002011.
|
|
|
PubMed id
|
|
|
|
|
|
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.
|
|
|
|
|
|
|
