5va4

TRIM-Cyclophilin A B-box 2 and coiled-coil chimera

spinqualitylabelsall models 5va4, resolution 2.31Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5va4 is a 1 chain structure with sequence from Aotus trivirgatus and Thermus thermophilus HB27. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.306Å Ligands: ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function SYS_THET2 Catalyzes the attachment of serine to tRNA(Ser). Is also probably able to aminoacylate tRNA(Sec) with serine, to form the misacylated tRNA L-seryl-tRNA(Sec), which will be further converted into selenocysteinyl-tRNA(Sec).[HAMAP-Rule:MF_00176]Q68KK2_AOTTR Publication Abstract from PubMed Restriction factors are intrinsic cellular defense proteins that have evolved to block microbial infections. Retroviruses such as HIV-1 are restricted by TRIM5 proteins, which recognize the viral capsid shell that surrounds, organizes, and protects the viral genome. TRIM5alpha uses a SPRY domain to bind capsids with low intrinsic affinity (KD >1 mM), and therefore requires higher-order assembly into a hexagonal lattice to generate sufficient avidity for productive capsid recognition. TRIMCyp, on the other hand, binds HIV-1 capsids through a cyclophilin A domain, which has a well-defined binding site and higher (KD approximately 10 muM) affinity for isolated capsid subunits. It has therefore been argued that TRIMCyp proteins may have dispensed with the need for higher-order assembly to function as antiviral factors. Here, we show that, consistent with its high degree of sequence similarity with TRIM5alpha, the TRIMCyp B-box 2 domain shares the same ability to self-associate and facilitate assembly of a TRIMCyp hexagonal lattice that can wrap about the HIV-1 capsid. We also show that under stringent experimental conditions, TRIMCyp-mediated restriction of HIV-1 is indeed dependent on higher-order assembly. Both forms of TRIM5 therefore use the same mechanism of avidity-driven capsid pattern recognition.IMPORTANCE Rhesus macaques and owl monkeys are highly resistant to HIV-1 infection due to the activity of TRIM5 restriction factors. The rhesus macaque TRIM5alpha protein blocks HIV-1 through a mechanism that requires self-assembly of a hexagonal TRIM5alpha lattice around the invading viral core. Lattice assembly amplifies very weak interactions between the TRIM5alpha SPRY domain and the HIV-1 capsid. Assembly also promotes dimerization of the TRIM5alpha RING E3 ligase domain, resulting in synthesis of polyubiquitin chains that mediate downstream steps of restriction. In contrast to rhesus TRIM5alpha, the owl monkey TRIM5 homolog, TRIMCyp, binds isolated HIV-1 CA subunits more tightly through its cyclophilin A domain, and was therefore thought to act independent of higher-order assembly. Here, we show that TRIMCyp shares the assembly properties of TRIM5alpha and that both forms of TRIM5 use the same mechanism of hexagonal lattice formation to promote viral recognition and restriction. A general model for retroviral capsid pattern recognition by TRIM5 proteins.,Wagner JM, Christensen DE, Bhattacharya A, Dawidziak DM, Roganowicz MD, Wan Y, Pumroy RA, Demeler B, Ivanov DN, Ganser-Pornillos BK, Sundquist WI, Pornillos O J Virol. 2017 Nov 29. pii: JVI.01563-17. doi: 10.1128/JVI.01563-17. PMID:29187540 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Proteopedia Page Contributors and Editors (what is this?)

OCA