4b3n
From Proteopedia
Crystal structure of rhesus TRIM5alpha PRY/SPRY domain
Structural highlights
FunctionMALE_ECOLI Involved in the high-affinity maltose membrane transport system MalEFGK. Initial receptor for the active transport of and chemotaxis toward maltooligosaccharides.TRIM5_MACMU Capsid-specific restriction factor that prevents infection from non-host-adapted retroviruses. Blocks viral replication early in the life cycle, after viral entry but before reverse transcription. In addition to acting as a capsid-specific restriction factor, also acts as a pattern recognition receptor that activates innate immune signaling in response to the retroviral capsid lattice. Binding to the viral capsid triggers its E3 ubiquitin ligase activity, and in concert with the heterodimeric ubiquitin conjugating enzyme complex UBE2V1-UBE2N (also known as UBC13-UEV1A complex) generates 'Lys-63'-linked polyubiquitin chains, which in turn are catalysts in the autophosphorylation of the MAP3K7/TAK1 complex (includes TAK1, TAB2, and TAB3). Activation of the MAP3K7/TAK1 complex by autophosphorylation results in the induction and expression of NF-kappa-B and MAPK-responsive inflammatory genes, thereby leading to an innate immune response in the infected cell. Restricts infection by human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV-agm).[1] [2] [3] Publication Abstract from PubMedTripartite motif protein isoform 5 alpha (TRIM5alpha) is a potent antiviral protein that restricts infection by HIV-1 and other retroviruses. TRIM5alpha recognizes the lattice of the retrovirus capsid through its B30.2 (PRY/SPRY) domain in a species-specific manner. Upon binding, TRIM5alpha induces premature disassembly of the viral capsid and activates the downstream innate immune response. We have determined the crystal structure of the rhesus TRIM5alpha PRY/SPRY domain that reveals essential features for capsid binding. Combined cryo-electron microscopy and biochemical data show that the monomeric rhesus TRIM5alpha PRY/SPRY, but not the human TRIM5alpha PRY/SPRY, can bind to HIV-1 capsid protein assemblies without causing disruption of the capsid. This suggests that the PRY/SPRY domain alone constitutes an important pattern-sensing component of TRIM5alpha that is capable of interacting with viral capsids of different curvatures. Our results provide molecular insights into the mechanisms of TRIM5alpha-mediated retroviral restriction. Structural insight into HIV-1 capsid recognition by rhesus TRIM5alpha.,Yang H, Ji X, Zhao G, Ning J, Zhao Q, Aiken C, Gronenborn AM, Zhang P, Xiong Y Proc Natl Acad Sci U S A. 2012 Nov 6;109(45):18372-7. doi:, 10.1073/pnas.1210903109. Epub 2012 Oct 22. PMID:23091002[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. Loading citation details.. Citations 13 reviews cite this structure No citations found References
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