| Title: |
The mechanism of Ca2+-dependent recognition of Alix by ALG-2: insights from X-ray crystal structures |
| Authors: |
Suzuki, Hironori; Kawasaki, Masato; Inuzuka, Tatsutoshi; Okumura, Mayumi; Kakiuchi, Takeshi; Shibata, Hideki; Wakatsuki, Soichi; Maki, Masatoshi |
| Source: |
Biochemical Society Transactions ; volume 37, issue 1, page 190-194 ; ISSN 0300-5127 1470-8752 |
| Publisher Information: |
Portland Press Ltd. |
| Publication Year: |
2009 |
| Description: |
Alix [ALG-2 (apoptosis-linked gene 2)-interacting protein X] was originally identified as a protein that interacts with ALG-2, a member of the penta-EF-hand Ca2+-binding protein family. ALG-2 binds to its C-terminal proline-rich region that contains four tandem repeats of PXY (where X represents an uncharged amino acid). Recent X-ray crystal structural analyses of the Ca2+-free and Ca2+-bound forms of ALG-2, as well as the complex with an Alix oligopeptide, have revealed a mechanism of Ca2+-dependent binding of ALG-2 to its target protein. Binding of Ca2+ to EF3 (third EF-hand) enables the side chain of Arg125, present in the loop connecting EF3 and EF4 (fourth EF-hand), to move sufficiently to make a primary hydrophobic pocket accessible to the critical PPYP (Pro-Pro-Tyr-Pro) motif in Alix, which partially overlaps with the GPP (Gly-Pro-Pro) motif for binding to Cep55 (centrosome protein of 55 kDa). The fact that ALG-2 forms a homodimer and each monomer has one peptide-binding site indicates the possibility that ALG-2 bridges two interacting proteins, including Alix and Tsg101 (tumour susceptibility gene 101), and functions as a Ca2+-dependent adaptor protein. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1042/bst0370190 |
| Availability: |
https://doi.org/10.1042/bst0370190; https://portlandpress.com/biochemsoctrans/article-pdf/37/1/190/545897/bst0370190.pdf |
| Accession Number: |
edsbas.20051595 |
| Database: |
BASE |