PDBsum entry: 1m4q

Peptide binding protein

PDB id: 1m4q

Contents

Protein chain

144 a.a. *

Ligands

PRO-GLU-PRO-THR-ALA-PRO-PRO-GLU-GLU

* Residue conservation analysis

PDB id:

1m4q

Name:

Peptide binding protein

Title:

Structure of the tsg101 uev domain in complex with a HIV-1 ptap "late domain" peptide, cns ensemble

Structure:

Tumor susceptibility gene 101 protein. Chain: a. Engineered: yes. Gag polyprotein. Chain: b. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: tumor susceptibility gene 101. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Human immunodeficiency virus 1. Organism_taxid: 11676. Strain: nl4-3.

NMR struc:

20 models

Authors:

O.Pornillos,S.L.Alam,D.R.Davis,W.I.Sundquist

Key ref:

O.Pornillos et al. (2002). Structure of the Tsg101 UEV domain in complex with the PTAP motif of the HIV-1 p6 protein. Nat Struct Biol, 9, 812-817. PubMed id: 12379843 DOI: 10.1038/nsb856

Date:

03-Jul-02 Release date: 06-Nov-02

Protein chain

Q99816  (TS101_HUMAN) -  Tumor susceptibility gene 101 protein

Seq: 390 a.a.

Struc: 144 a.a.

 Gene Ontology (GO) functional annotation 

• Biological process: protein transport (4 terms)
• Biochemical function: small conjugating protein ligase activity (1 term)

DOI no: 10.1038/nsb856

Nat Struct Biol 9:812-817 (2002)

PubMed id: 12379843

Structure of the Tsg101 UEV domain in complex with the PTAP motif of the HIV-1 p6 protein.

O.Pornillos, S.L.Alam, D.R.Davis, W.I.Sundquist.

ABSTRACT

The structural proteins of HIV and Ebola display PTAP peptide motifs (termed 'late domains') that recruit the human protein Tsg101 to facilitate virus budding. Here we present the solution structure of the UEV (ubiquitin E2 variant) binding domain of Tsg101 in complex with a PTAP peptide that spans the late domain of HIV-1 p6(Gag). The UEV domain of Tsg101 resembles E2 ubiquitin-conjugating enzymes, and the PTAP peptide binds in a bifurcated groove above the vestigial enzyme active site. Each PTAP residue makes important contacts, and the Ala 9-Pro 10 dipeptide binds in a deep pocket of the UEV domain that resembles the X-Pro binding pockets of SH3 and WW domains. The structure reveals the molecular basis of HIV PTAP late domain function and represents an attractive starting point for the design of novel inhibitors of virus budding.

Selected figure(s)

Figure 3.
Figure 3. Molecular recognition in the Tsg101 UEV−PTAP peptide complex. a, Summary of contacts^53 between the Tsg101 UEV domain and the PTAP peptide (dark green). Hydrogen bonding interactions shown for O of Thr 8 were not observed in all calculated structures. b, Stereo view of the PTAP peptide (dark green) in its binding groove on Tsg101 UEV. The 'Pro' pocket, which binds Pro 7 of PTAP (residues 7−10) from p6, and the 'Ala-Pro' pocket, which binds the Ala 9-Pro 10 dipeptide, are circled in blue and magenta, respectively. PTAP peptide binding buries a total surface area of 1,350 Å^2. The ubiquitin-binding surface of Tsg101 UEV is indicated in black.

Figure 4.
Figure 4. Proline recognition by Tsg101 UEV. Expanded views of the a, Pro and b, Ala-Pro binding pockets, viewed along the binding groove from the N-terminal end of the peptide. c, Similarities between X-Pro proline recognition in the Tsg101 UEV (dark green), SH3 (yellow) and WW (orange) domains. In each case, 'key' Pro residues of bound ligands are sandwiched between two aromatic rings.

The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Biol (2002, 9, 812-817) copyright 2002.

Figures were selected by the author.