3WXA

X-ray crystal structural analysis of the complex between ALG-2 and Sec31A peptide

Summary for 3WXA

• Entry DOI: 10.2210/pdb3wxa/pdb
• Descriptor: Programmed cell death protein 6, Protein transport protein Sec31A, ZINC ION, ... (4 entities in total)
• Functional Keywords: penta-ef-hand protein, endoplasmic reticulum, membrane, transport, apoptosis, calcium binding, apoptosis-transport protein complex, apoptosis/transport protein
• Biological source: Homo sapiens (human); More
• Cellular location: Endoplasmic reticulum membrane ; Peripheral membrane protein : O75340; Cytoplasm : O94979
• Total number of polymer chains: 4
• Total formula weight: 43527.99

Authors

Takahashi, T.,Suzuki, H.,Kawasaki, M.,Shibata, H.,Wakatsuki, S.,Maki, M. (deposition date: 2014-07-29, release date: 2015-03-11, Last modification date: 2023-11-08)

Primary citation

Takahashi, T.,Kojima, K.,Zhang, W.,Sasaki, K.,Ito, M.,Suzuki, H.,Kawasaki, M.,Wakatsuki, S.,Takahara, T.,Shibata, H.,Maki, M.
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, 2015

PubMed 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.

PubMed: 25667979
DOI: 10.3390/ijms16023677

Experimental method

X-RAY DIFFRACTION (2.36 Å)