Modulation of retroviral restriction and proteasorne inhibitor-resistant turnover by changes in the TRIM5α B-Box 2 domain

被引:64
作者
Diaz-Griffero, Felipe
Kar, Alak
Perron, Michel
Xiang, Shi-Hua
Javanbakht, Hassan
Li, Xing
Sodroski, Joseph
机构
[1] Harvard Univ, Sch Med, Dept Pathol,Dept Canc Immunol & AIDS, Dana Farber Canc Inst, Boston, MA 02115 USA
[2] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA
关键词
D O I
10.1128/JVI.00703-07
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
An intact B-box 2 domain is essential for the antiretroviral activity of TRIM5 alpha. We modeled the structure of the B-box 2 domain of TRIM5 alpha based on the existing three-dimensional structure of the B-box 2 domain of human TRIM29. Using this model, we altered the residues predicted to be exposed on the surface of this globular structure. Most of the alanine substitutions in these residues exerted little effect on the antiretroviral activity of human TRIM5c alpha(hu). or rhesus monkey TRIM5C alpha(rh). However, alteration of arginine 119 of TRIM5 alpha(hu). or the corresponding arginine 121 of TRIM5 alpha(rh), diminished the abilities of the proteins to restrict retroviral infection without affecting trimerization or recognition of the viral capsid. The abilities of these functionally defective TRIM5 alpha proteins to accelerate the uncoating of the targeted retroviral capsid were abolished. Removal of the positively charged side chain from B-box 2 arginines 119/120/121 resulted in diminished proteasome-independent turnover of TRIM5 alpha and the related restriction factor TRIMCyp. However, testing of an array of mutants revealed that the rapid turnover and retroviral restriction functions of this B-box 2 region are separable.
引用
收藏
页码:10362 / 10378
页数:17
相关论文
共 42 条
[1]   RING fingers and B-boxes: zinc-binding protein-protein interaction domains [J].
Borden, KLB .
BIOCHEMISTRY AND CELL BIOLOGY, 1998, 76 (2-3) :351-358
[2]   Trim5α accelerates degradation of cytosolic capsid associated with productive HIV-1 entry [J].
Chatterji, Udayan ;
Bobardt, Michael D. ;
Gaskill, Peter ;
Sheeter, Dennis ;
Fox, Howard ;
Gallay, Philippe A. .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2006, 281 (48) :37025-37033
[3]   Endocytosis is a critical step in entry of subgroup B avian leukosis viruses [J].
Diaz-Griffero, F ;
Hoschander, SA ;
Brojatsch, J .
JOURNAL OF VIROLOGY, 2002, 76 (24) :12866-12876
[4]   Requirements for capsid-binding and an effector function in TRIMCyp-mediated restriction of HIV-1 [J].
Diaz-Griffero, Felipe ;
Vandegraaff, Nick ;
Li, Yuan ;
McGee-Estrada, Kathleen ;
Stremlau, Matthew ;
Welikala, Sohanya ;
Si, Zhihai ;
Engelman, Alan ;
Sodroski, Joseph .
VIROLOGY, 2006, 351 (02) :404-419
[5]   Rapid turnover and polyubiquitylation of the retroviral restriction factor TRIM5 [J].
Diaz-Griffero, Felipe ;
Li, Xing ;
Javanbakht, Hassan ;
Song, Byeongwoon ;
Welikala, Sohanya ;
Stremlau, Matthew ;
Sodroski, Joseph .
VIROLOGY, 2006, 349 (02) :300-315
[6]   MODELLER: Generation and refinement of homology-based protein structure models [J].
Fiser, A ;
Sali, A .
MACROMOLECULAR CRYSTALLOGRAPHY, PT D, 2003, 374 :461-491
[7]   Assembly and analysis of conical models for the HIV-1 core [J].
Ganser, BK ;
Li, S ;
Klishko, VY ;
Finch, JT ;
Sundquist, WI .
SCIENCE, 1999, 283 (5398) :80-83
[8]   Assembly properties of the human immunodeficiency virus type 1 CA protein [J].
Ganser-Pornillos, BK ;
von Schwedler, UK ;
Stray, KM ;
Aiken, C ;
Sundquist, WI .
JOURNAL OF VIROLOGY, 2004, 78 (05) :2545-2552
[9]   Retrovirus resistance factors Ref1 and Lv1 are species-specific variants of TRIM5α [J].
Hatziioannou, T ;
Perez-Caballero, D ;
Yang, A ;
Cowan, S ;
Bieniasz, PD .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (29) :10774-10779
[10]   TRIM11 binds to and destabilizes a key component of the activator-mediated cofactor complex (ARC105) through the ubiquitin-proteasome system [J].
Ishikawa, Hideaki ;
Tachikawa, Hiroyuki ;
Miura, Yutaka ;
Takahashi, Nobuhiro .
FEBS LETTERS, 2006, 580 (20) :4784-4792