3wxa
From Proteopedia
X-ray crystal structural analysis of the complex between ALG-2 and Sec31A peptide
Structural highlights
Disease[SC31A_HUMAN] A chromosomal aberration involving SEC31A is associated with inflammatory myofibroblastic tumors (IMTs). Translocation t(2;4)(p23;q21) with ALK. Function[PDCD6_HUMAN] Calcium-binding protein required for T-cell receptor-, Fas-, and glucocorticoid-induced cell death. May mediate Ca(2+)-regulated signals along the death pathway (By similarity). Calcium-dependent adapter necessary for the association between PDCD6IP and TSG101. Interaction with DAPK1 can accelerate apoptotic cell death by increasing caspase-3 activity.[1] [2] [SC31A_HUMAN] Component of the coat protein complex II (COPII) which promotes the formation of transport vesicles from the endoplasmic reticulum (ER). The coat has two main functions, the physical deformation of the endoplasmic reticulum membrane into vesicles and the selection of cargo molecules (By similarity). Publication Abstract from PubMedALG-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. Structural Analysis of the Complex between Penta-EF-Hand ALG-2 Protein and Sec31A Peptide Reveals a Novel Target Recognition Mechanism of ALG-2.,Takahashi T, Kojima K, Zhang W, Sasaki K, Ito M, Suzuki H, Kawasaki M, Wakatsuki S, Takahara T, Shibata H, Maki M Int J Mol Sci. 2015 Feb 6;16(2):3677-99. doi: 10.3390/ijms16023677. PMID:25667979[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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