PDBsum entry 3wxa

Apoptosis/transport protein

PDB id: 3wxa

Contents

Protein chains

167 a.a.

12 a.a.

Metals

_ZN ×10

Waters ×28

PDB id:

3wxa

Name:

Apoptosis/transport protein

Title:

X-ray crystal structural analysis of the complex between alg-2 and sec31a peptide

Structure:

Programmed cell death protein 6. Chain: a, b. Fragment: unp residues 20-191. Synonym: apoptosis-linked gene 2 protein, probable calcium-binding protein alg-2. Engineered: yes. Protein transport protein sec31a. Chain: c, d. Fragment: alg-2 binding site, unp residues 837-848.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: pdcd6, alg2. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Other_details: this sequence occurs naturally in humans.

Resolution:

2.36Å R-factor: 0.230 R-free: 0.263

Authors:

T.Takahashi,H.Suzuki,M.Kawasaki,H.Shibata,S.Wakatsuki,M.Maki

Key ref:

T.Takahashi et al. (2015). Structural analysis of the complex between penta-EF-hand ALG-2 protein and Sec31A peptide reveals a novel target recognition mechanism of ALG-2. Int J Mol Sci, 16, 3677-3699. PubMed id: 25667979 DOI: 10.3390/ijms16023677

Date:

29-Jul-14 Release date: 11-Mar-15

Protein chains

O75340  (PDCD6_HUMAN) -  Programmed cell death protein 6 from Homo sapiens

Seq: 191 a.a.

Struc: 167 a.a.

Protein chains

O94979  (SC31A_HUMAN) -  Protein transport protein Sec31A from Homo sapiens

Seq: 1220 a.a.

Struc: 12 a.a.

DOI no: 10.3390/ijms16023677

Int J Mol Sci 16:3677-3699 (2015)

PubMed id: 25667979

Structural analysis of the complex between penta-EF-hand ALG-2 protein and Sec31A peptide reveals a novel target recognition mechanism of ALG-2.

T.Takahashi, K.Kojima, W.Zhang, K.Sasaki, M.Ito, H.Suzuki, M.Kawasaki, S.Wakatsuki, T.Takahara, H.Shibata, M.Maki.

ABSTRACT

ALG-2, a 22-kDa penta-EF-hand protein, is involved in cell death, signal transduction, membrane trafficking, etc., by interacting with various proteins in mammalian cells in a Ca2+-dependent manner. Most known ALG-2-interacting proteins contain proline-rich regions in which either PPYPXnYP (type 1 motif) or PXPGF (type 2 motif) is commonly found. Previous X-ray crystal structural analysis of the complex between ALG-2 and an ALIX peptide revealed that the peptide binds to the two hydrophobic pockets. In the present study, we resolved the crystal structure of the complex between ALG-2 and a peptide of Sec31A (outer shell component of coat complex II, COPII; containing the type 2 motif) and found that the peptide binds to the third hydrophobic pocket (Pocket 3). While amino acid substitution of Phe85, a Pocket 3 residue, with Ala abrogated the interaction with Sec31A, it did not affect the interaction with ALIX. On the other hand, amino acid substitution of Tyr180, a Pocket 1 residue, with Ala caused loss of binding to ALIX, but maintained binding to Sec31A. We conclude that ALG-2 recognizes two types of motifs at different hydrophobic surfaces. Furthermore, based on the results of serial mutational analysis of the ALG-2-binding sites in Sec31A, the type 2 motif was newly defined.