PDBsum entry 4z8l

Viral protein/vpx-binding protein

PDB id: 4z8l

Contents

Protein chains

305 a.a.

79 a.a.

92 a.a.

95 a.a.

Metals

_ZN ×2

Waters ×114

PDB id:

4z8l

Name:

Viral protein/vpx-binding protein

Title:

Crystal structure of dcaf1/siv-mnd vpx/mnd samhd1 ntd ternary complex

Structure:

Protein vprbp. Chain: a, d. Fragment: unp residues 1057-1396. Synonym: ddb1- and cul4-associated factor 1,HIV-1 vpr-binding protein,vprbp,serine/threonine-protein kinase vprbp,vpr-interacting protein. Engineered: yes. Vpx protein. Chain: b, e.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: vprbp, dcaf1, kiaa0800, rip. Expressed in: baculoviridae. Expression_system_taxid: 10442. Simian immunodeficiency virus. Siv. Organism_taxid: 11723.

Resolution:

2.60Å R-factor: 0.202 R-free: 0.228

Authors:

L.M.Koharudin,Y.Wu,G.Calero,J.Ahn,A.M.Gronenborn

Key ref:

Y.Wu et al. (2015). Structural Basis of Clade-specific Engagement of SAMHD1 (Sterile α Motif and Histidine/Aspartate-containing Protein 1) Restriction Factors by Lentiviral Viral Protein X (Vpx) Virulence Factors. J Biol Chem, 290, 17935-17945. PubMed id: 26045556 DOI: 10.1074/jbc.M115.665513

Date:

09-Apr-15 Release date: 17-Jun-15

Protein chains

Q9Y4B6  (DCAF1_HUMAN) -  DDB1- and CUL4-associated factor 1 from Homo sapiens

Seq: 1507 a.a.

Struc: 305 a.a.

Protein chains

Q7ZB17  (Q7ZB17_SIV) -  Protein Vpr from Simian immunodeficiency virus

Seq: 99 a.a.

Struc: 79 a.a.

Protein chain

H6WEA4  (H6WEA4_MANSP) -  Deoxynucleoside triphosphate triphosphohydrolase SAMHD1 from Mandrillus sphinx

Seq: 626 a.a.

Struc: 92 a.a.

Protein chain

H6WEA4  (H6WEA4_MANSP) -  Deoxynucleoside triphosphate triphosphohydrolase SAMHD1 from Mandrillus sphinx

Seq: 626 a.a.

Struc: 95 a.a.

Enzyme reactions

• Enzyme class: Chains A, D: E.C.2.7.11.1 - non-specific serine/threonine protein kinase.
• Reaction:
  1. L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H⁺
  2. L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H⁺

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

reference

DOI no: 10.1074/jbc.M115.665513

J Biol Chem 290:17935-17945 (2015)

PubMed id: 26045556

Structural Basis of Clade-specific Engagement of SAMHD1 (Sterile α Motif and Histidine/Aspartate-containing Protein 1) Restriction Factors by Lentiviral Viral Protein X (Vpx) Virulence Factors.

Y.Wu, L.M.Koharudin, J.Mehrens, M.DeLucia, C.H.Byeon, I.J.Byeon, G.Calero, J.Ahn, A.M.Gronenborn.

ABSTRACT

Sterile α motif (SAM) and histidine/aspartate (HD)-containing protein 1 (SAMHD1) restricts human/simian immunodeficiency virus infection in certain cell types and is counteracted by the virulence factor Vpx. Current evidence indicates that Vpx recruits SAMHD1 to the Cullin4-Ring Finger E3 ubiquitin ligase (CRL4) by facilitating an interaction between SAMHD1 and the substrate receptor DDB1- and Cullin4-associated factor 1 (DCAF1), thereby targeting SAMHD1 for proteasome-dependent down-regulation. Host-pathogen co-evolution and positive selection at the interfaces of host-pathogen complexes are associated with sequence divergence and varying functional consequences. Two alternative interaction interfaces are used by SAMHD1 and Vpx: the SAMHD1 N-terminal tail and the adjacent SAM domain or the C-terminal tail proceeding the HD domain are targeted by different Vpx variants in a unique fashion. In contrast, the C-terminal WD40 domain of DCAF1 interfaces similarly with the two above complexes. Comprehensive biochemical and structural biology approaches permitted us to delineate details of clade-specific recognition of SAMHD1 by lentiviral Vpx proteins. We show that not only the SAM domain but also the N-terminal tail engages in the DCAF1-Vpx interaction. Furthermore, we show that changing the single Ser-52 in human SAMHD1 to Phe, the residue found in SAMHD1 of Red-capped monkey and Mandrill, allows it to be recognized by Vpx proteins of simian viruses infecting those primate species, which normally does not target wild type human SAMHD1 for degradation.