Imperial College London
Alternate

Emeritus ProfessorJonathanStoye

Faculty of Medicine, Department of Infectious Disease

Emeritus Professor of Endogenous Retroviruses
 
 
 
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Contact

 

j.stoye Website

 
 
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Location

 

Francis Crick InstituteThe Francis Crick Institute

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Summary

 

Publications

Citation

BibTex format

@article{Goldstone:2014:10.1073/pnas.1402448111,
author = {Goldstone, DC and Walker, PA and Calder, LJ and Coombs, PJ and Kirkpatrick, J and Ball, NJ and Hilditch, L and Yap, MW and Rosenthal, PB and Stoye, JP and Taylor, IA},
doi = {10.1073/pnas.1402448111},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
pages = {9609--9614},
title = {Structural studies of postentry restriction factors reveal antiparallel dimers that enable avid binding to the HIV-1 capsid lattice},
url = {http://dx.doi.org/10.1073/pnas.1402448111},
volume = {111},
year = {2014}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Restriction factors (RFs) form important components of host defenses to retroviral infection. The Fv1, Trim5α, and TrimCyp RFs contain N-terminal dimerization and C-terminal specificity domains that target assembled retroviral capsid (CA) proteins enclosing the viral core. However, the molecular detail of the interaction between RFs and their CA targets is unknown. Therefore, we have determined the crystal structure of the B-box and coiled-coil (BCC) region from Trim5α and used small-angle X-ray scattering to examine the solution structure of Trim5α BCC, the dimerization domain of Fv1 (Fv1Ntd), and the hybrid restriction factor Fv1Cyp comprising Fv1NtD fused to the HIV-1 binding protein Cyclophilin A (CypA). These data reveal that coiled-coil regions of Fv1 and Trim5α form extended antiparallel dimers. In Fv1Cyp, two CypA moieties are located at opposing ends, creating a molecule with a dumbbell appearance. In Trim5α, the B-boxes are located at either end of the coiled-coil, held in place by interactions with a helical motif from the L2 region of the opposing monomer. A comparative analysis of Fv1Cyp and CypA binding to a preformed HIV-1 CA lattice reveals how RF dimerization enhances the affinity of interaction through avidity effects. We conclude that the antiparallel organization of the NtD regions of Fv1 and Trim5α dimers correctly positions C-terminal specificity and N-terminal effector domains and facilitates stable binding to adjacent CA hexamers in viral cores.
AU  - Goldstone,DC
AU  - Walker,PA
AU  - Calder,LJ
AU  - Coombs,PJ
AU  - Kirkpatrick,J
AU  - Ball,NJ
AU  - Hilditch,L
AU  - Yap,MW
AU  - Rosenthal,PB
AU  - Stoye,JP
AU  - Taylor,IA
DO  - 10.1073/pnas.1402448111
EP  - 9614
PY  - 2014///
SN  - 0027-8424
SP  - 9609
TI  - Structural studies of postentry restriction factors reveal antiparallel dimers that enable avid binding to the HIV-1 capsid lattice
T2  - Proceedings of the National Academy of Sciences of the United States of America
UR  - http://dx.doi.org/10.1073/pnas.1402448111
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000338118900065&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://www.pnas.org/content/111/26/9609
VL  - 111
ER  -
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