4TN3

Structure of the BBox-Coiled-coil region of Rhesus Trim5alpha

4TN3 の概要

• エントリーDOI: 10.2210/pdb4tn3/pdb
• 分子名称: TRIM5/cyclophilin A fusion protein/T4 Lysozyme chimera, ZINC ION (2 entities in total)
• 機能のキーワード: trim protein coiled-coil scaffold retroviral restriction factor, antiviral protein
• 由来する生物種: Macaca mulatta (Rhesus macaque); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 92931.19

構造登録者

Kirkpatrick, J.J.,Stoye, J.P.,Taylor, I.A.,Goldstone, D.C. (登録日: 2014-06-03, 公開日: 2014-07-16, 最終更新日: 2023-09-27)

主引用文献

Goldstone, D.C.,Walker, P.A.,Calder, L.J.,Coombs, P.J.,Kirkpatrick, J.,Ball, N.J.,Hilditch, L.,Yap, M.W.,Rosenthal, P.B.,Stoye, J.P.,Taylor, I.A.
Structural studies of postentry restriction factors reveal antiparallel dimers that enable avid binding to the HIV-1 capsid lattice.
Proc.Natl.Acad.Sci.USA, 111:9609-9614, 2014

PubMed Abstract: 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.

PubMed: 24979782
DOI: 10.1073/pnas.1402448111

実験手法

X-RAY DIFFRACTION (3.1989 Å)