1hqv
From Proteopedia
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STRUCTURE OF APOPTOSIS-LINKED PROTEIN ALG-2
Overview
BACKGROUND: The Ca2+ binding apoptosis-linked gene-2 (ALG-2) protein acts, as a proapoptotic factor in a variety of cell lines and is required either, downstream or independently of caspases for apoptosis to occur. ALG-2, belongs to the penta-EF-hand (PEF) protein family and has two, high-affinity and one low-affinity Ca2+ binding sites. Like other PEF, proteins, its N terminus contains a Gly/Pro-rich segment. Ca2+ binding is, required for the interaction with the target protein, ALG-2 interacting, protein 1 (AIP1). RESULTS: We present the 2.3 A resolution crystal, structure of Ca2+-Ioaded des1-20ALG-2 (aa 21-191), which was obtained by, limited proteolysis of recombinant ALG-2 with elastase. The molecule, contains eight alpha helices that fold into five EF-hands, and, similar to, other members of this protein family, the molecule forms dimers. Ca2+ ions, bind to EF1, EF3, and, surprisingly, to EF5. In the related proteins, calpain and grancalcin, the EF5 does not bind Ca2+ and is thought to, primarily facilitate dimerization. Most importantly, the conformation of, des1-20ALG-2 is significantly different from that of calpain and, grancalcin. This difference can be described as a rigid body rotation of, EF1-2 relative to EF4-5 and the dimer interface, with a hinge within the, EF3 loop. An electron density, which is interpreted as a hydrophobic, Gly/Pro-rich decapeptide that is possibly derived from the cleaved N, terminus, was found in a hydrophobic cleft between these two halves of the, molecule. CONCLUSIONS: A different relative orientation of the N- and, C-terminal halves of des1-20ALG-2 in the presence of Ca2+ and the peptide, as compared to other Ca2+loaded PEF proteins changes substantially the, shape of the molecule, exposing a hydrophobic patch on the surface for, peptide binding and a large cleft near the dimer interface. We postulate, that the binding of a Gly/ Pro-rich peptide in the presence of Ca2+, induces a conformational rearrangement in ALG-2, and that this mechanism, is common to other PEF proteins.
About this Structure
1HQV is a Single protein structure of sequence from Mus musculus with CA as ligand. Full crystallographic information is available from OCA.
Reference
Structure of apoptosis-linked protein ALG-2: insights into Ca2+-induced changes in penta-EF-hand proteins., Jia J, Tarabykina S, Hansen C, Berchtold M, Cygler M, Structure. 2001 Apr 4;9(4):267-75. PMID:11525164
Page seeded by OCA on Tue Nov 20 16:45:42 2007
