PDBsum entry: 1jwf

Protein transport

PDB id: 1jwf

Contents

Protein chain

139 a.a. *

Waters ×34

* Residue conservation analysis

PDB id:

1jwf

Name:

Protein transport

Title:

Crystal structure of human gga1 vhs domain.

Structure:

Adp-ribosylation factor binding protein gga1. Chain: a. Fragment: vhs domain(n-terminal domain). Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.10Å R-factor: 0.223 R-free: 0.261

Authors:

T.Shiba,H.Takatsu,T.Nogi,N Matsugaki,M.Kawasaki,N.Igarashi, M.Suzuki,R.Kato,T.Earnest,K.Nakayama,S.Wakatsuki

Key ref:

T.Shiba et al. (2002). Structural basis for recognition of acidic-cluster dileucine sequence by GGA1. Nature, 415, 937-941. PubMed id: 11859376 DOI: 10.1038/415937a

Date:

04-Sep-01 Release date: 06-Mar-02

Protein chain

Q9UJY5  (GGA1_HUMAN) -  ADP-ribosylation factor-binding protein GGA1

Seq: 639 a.a.

Struc: 139 a.a.

 Gene Ontology (GO) functional annotation 

• Biological process: intracellular protein transport (1 term)

DOI no: 10.1038/415937a

Nature 415:937-941 (2002)

PubMed id: 11859376

Structural basis for recognition of acidic-cluster dileucine sequence by GGA1.

T.Shiba, H.Takatsu, T.Nogi, N.Matsugaki, M.Kawasaki, N.Igarashi, M.Suzuki, R.Kato, T.Earnest, K.Nakayama, S.Wakatsuki.

ABSTRACT

GGAs (Golgi-localizing, gamma-adaptin ear homology domain, ARF-interacting proteins) are critical for the transport of soluble proteins from the trans-Golgi network (TGN) to endosomes/lysosomes by means of interactions with TGN-sorting receptors, ADP-ribosylation factor (ARF), and clathrin. The amino-terminal VHS domains of GGAs form complexes with the cytoplasmic domains of sorting receptors by recognizing acidic-cluster dileucine (ACLL) sequences. Here we report the X-ray structure of the GGA1 VHS domain alone, and in complex with the carboxy-terminal peptide of cation-independent mannose 6-phosphate receptor containing an ACLL sequence. The VHS domain forms a super helix with eight alpha-helices, similar to the VHS domains of TOM1 and Hrs. Unidirectional movements of helices alpha6 and alpha8, and some of their side chains, create a set of electrostatic and hydrophobic interactions for correct recognition of the ACLL peptide. This recognition mechanism provides the basis for regulation of protein transport from the TGN to endosomes/lysosomes, which is shared by sortilin and low-density lipoprotein receptor-related protein.

Selected figure(s)

Figure 2.
Figure 2: Surface representation of the VHS domain interacting with the CI-MPR ACLL peptide. The surfaces are coloured according to the electrostatic surface potential in a -d (blue, positive; red, negative; scale (-10 to +10) kT e^-1) and hydorophobicity in e, f (green). a, The VHS domain (in complex form) without the peptide. b, With the peptide in the same view as in a. c, The peptide bound to the VHS domain. The peptide is shown as sticks, and the basic residues interacting with the peptide are labelled. d, The other side of the peptide. e, The peptide bound to the VHS domain (same view as in c). f, Hydrophobicity of the other side of the peptide (same view as in d). c, d and e, f are shown as open-book pairs.

Figure 3.
Figure 3: Peptide binding diagram. The main chain and the side chains of the ACLL peptide are shown in grey, and side chains involved in the specific interactions are shown by ball-and-stick models. VHS domain residues in helices 6 and 8 are shown in green and orange, respectively, where residues involved in the hydrogen bond or the charged interaction are shown by ball-and-stick models and those in the hydrophobic interaction are indicated only by text. In the ball-and-stick models, each atom is coloured as follows: carbon, grey; nitrogen, blue; oxygen, red. Hydrogen bonds or charged interactions are indicated by green dotted lines, and hydrophobic interactions by red dotted lines with a 'starburst' around each atom or residue.

The above figures are reprinted by permission from Macmillan Publishers Ltd: Nature (2002, 415, 937-941) copyright 2002.

Figures were selected by an automated process.