PDBsum entry: 1jpl

Signaling protein

PDB id: 1jpl

Contents

Protein chains

161 a.a. *

Ligands

SER-ASP-GLU-ASP-LEU-LEU-HIS-ILE ×3

ASP-SER-ASP-GLU-ASP-LEU-LEU-HIS-ILE

Waters ×237

* Residue conservation analysis

PDB id:

1jpl

Name:

Signaling protein

Title:

Gga3 vhs domain complexed with c-terminal peptide from cation-independent mannose 6-phosphate receptor

Structure:

Adp-ribosylation factor binding protein gga3. Chain: a, b, c, d. Fragment: vhs domain. Engineered: yes. Cation-independent mannose 6-phosphate receptor. Chain: e, f, g, h. Fragment: c-terminal peptide. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: gga3. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Synthetic: yes. Other_details: the peptide was chemically synthesized.

Biol. unit:

Dimer (from PQS)

Resolution:

2.40Å R-factor: 0.213 R-free: 0.257

Authors:

S.Misra,R.Puertollano,J.S.Bonifacino,J.H.Hurley

Key ref:

S.Misra et al. (2002). Structural basis for acidic-cluster-dileucine sorting-signal recognition by VHS domains. Nature, 415, 933-937. PubMed id: 11859375 DOI: 10.1038/415933a

Date:

02-Aug-01 Release date: 27-Feb-02

Protein chains

Q9NZ52  (GGA3_HUMAN) -  ADP-ribosylation factor-binding protein GGA3

Seq: 723 a.a.

Struc: 161 a.a.

 Gene Ontology (GO) functional annotation 

• Biological process: intracellular protein transport (1 term)

DOI no: 10.1038/415933a

Nature 415:933-937 (2002)

PubMed id: 11859375

Structural basis for acidic-cluster-dileucine sorting-signal recognition by VHS domains.

S.Misra, R.Puertollano, Y.Kato, J.S.Bonifacino, J.H.Hurley.

ABSTRACT

Specific sorting signals direct transmembrane proteins to the compartments of the endosomal-lysosomal system. Acidic-cluster-dileucine signals present within the cytoplasmic tails of sorting receptors, such as the cation-independent and cation-dependent mannose-6-phosphate receptors, are recognized by the GGA (Golgi-localized, gamma-ear-containing, ADP-ribosylation-factor-binding) proteins. The VHS (Vps27p, Hrs and STAM) domains of the GGA proteins are responsible for the highly specific recognition of these acidic-cluster-dileucine signals. Here we report the structures of the VHS domain of human GGA3 complexed with signals from both mannose-6-phosphate receptors. The signals bind in an extended conformation to helices 6 and 8 of the VHS domain. The structures highlight an Asp residue separated by two residues from a dileucine sequence as critical recognition elements. The side chains of the Asp-X-X-Leu-Leu sequence interact with subsites consisting of one electropositive and two shallow hydrophobic pockets, respectively. The rigid spatial alignment of the three binding subsites leads to high specificity.

Selected figure(s)

Figure 1.
Figure 1: Structures of the GGA3-VHS domain bound to signal peptides. a, Representative acidic-cluster-dileucine motifs. The first four sequences bind GGA-VHS domains7 -10, the last three do not7. b, Structure of the VHS domain with CI-MPR sorting signal (ball-and-stick model) bound between helices 6 and 8. The first and last visible residues of the CI-MPR peptide are labelled. c, Molecular surface of the VHS domain, coloured by electrostatic potential. Saturated blue and red areas are at +10kT and -10kT respectively. The CI-MPR peptide is shown in green. d, e, Calculated 2f[o] - f[c] omit maps for the CI-MPR (d) and CD-MPR (e) sorting signals, contoured at 1.0 and 0.9 , respectively. f, Scheme highlighting the primary determinants of peptide binding to the GGA-VHS domains.

Figure 2.
Figure 2: Molecular details of the interactions between the acidic-cluster-dileucine motifs and their binding site on the VHS domain. a, b, Ball-and-stick representations of the CI-MPR (a) and CD-MPR (b) sorting sequences, and the VHS residues with which they interact. Oxygen, nitrogen and sulphur atoms are coloured red, blue and green, respectively. Carbon atoms of the signal sequences are grey, and carbon atoms from VHS domain residues are coloured gold. Hydrogen bonds and salt-bridge interactions are shown as dashed lines. The arrows designate close-up views of the appropriate sites. Close-ups are not shown in b because the sites are very similar to the corresponding sites in a.

The above figures are reprinted by permission from Macmillan Publishers Ltd: Nature (2002, 415, 933-937) copyright 2002.

Figures were selected by the author.