PDBsum entry 4tn3

Antiviral protein

PDB id: 4tn3

Contents

Protein chains

359 a.a.

362 a.a.

Metals

_ZN ×4

PDB id:

4tn3

Name:

Antiviral protein

Title:

Structure of the bbox-coiled-coil region of rhesus trim5alpha

Structure:

Trim5/cyclophilin a fusion protein/t4 lysozyme chimera. Chain: a, b. Synonym: lysis protein,lysozyme,muramidase. Engineered: yes

Source:

Macaca mulatta, enterobacteria phage t4. Rhesus macaque. Organism_taxid: 9544, 10665. Gene: trimcyp. Expressed in: escherichia coli. Expression_system_taxid: 469008, 562.

Resolution:

3.20Å R-factor: 0.261 R-free: 0.316

Authors:

J.J.Kirkpatrick,J.P.Stoye,I.A.Taylor,D.C.Goldstone

Key ref:

D.C.Goldstone et al. (2014). Structural studies of postentry restriction factors reveal antiparallel dimers that enable avid binding to the HIV-1 capsid lattice. Proc Natl Acad Sci U S A, 111, 9609-9614. PubMed id: 24979782 DOI: 10.1073/pnas.1402448111

Date:

03-Jun-14 Release date: 16-Jul-14

Protein chain

G9MAP5  (G9MAP5_MACMU) -  Peptidyl-prolyl cis-trans isomerase A (Fragment) from Macaca mulatta

Seq: 468 a.a.

Struc: 359 a.a.*

Protein chain

P00720  (ENLYS_BPT4) -  Endolysin from Enterobacteria phage T4

Seq: 164 a.a.

Struc: 359 a.a.*

Protein chain

G9MAP5  (G9MAP5_MACMU) -  Peptidyl-prolyl cis-trans isomerase A (Fragment) from Macaca mulatta

Seq: 468 a.a.

Struc: 362 a.a.*

Protein chain

P00720  (ENLYS_BPT4) -  Endolysin from Enterobacteria phage T4

Seq: 164 a.a.

Struc: 362 a.a.*

* PDB and UniProt seqs differ at 326 residue positions (black crosses)

Enzyme reactions

• Enzyme class 1: Chains A, B: E.C.3.2.1.17 - lysozyme.
• Reaction: Hydrolysis of the 1,4-beta-linkages between N-acetyl-D-glucosamine and N-acetylmuramic acid in peptidoglycan heteropolymers of the prokaryotes cell walls.
• Enzyme class 2: Chains A, B: E.C.5.2.1.8 - peptidylprolyl isomerase.
• Reaction: [protein]-peptidylproline (omega=180) = [protein]-peptidylproline (omega=0)

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

Added reference

DOI no: 10.1073/pnas.1402448111

Proc Natl Acad Sci U S A 111:9609-9614 (2014)

PubMed id: 24979782

Structural studies of postentry restriction factors reveal antiparallel dimers that enable avid binding to the HIV-1 capsid lattice.

D.C.Goldstone, P.A.Walker, L.J.Calder, P.J.Coombs, J.Kirkpatrick, N.J.Ball, L.Hilditch, M.W.Yap, P.B.Rosenthal, J.P.Stoye, I.A.Taylor.

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.