ALG-2(a gene product of PDCD6) is a 22-kD protein containing five serially repetitive EF-hand structures and belongs to the penta-EF-hand(PEF) family,including the subunits of typical calpains.ALG-2 is the most conser...ALG-2(a gene product of PDCD6) is a 22-kD protein containing five serially repetitive EF-hand structures and belongs to the penta-EF-hand(PEF) family,including the subunits of typical calpains.ALG-2 is the most conserved protein among the PEF family members and its homologs are widely found in eukaryotes.X-ray crystal structures of various PEF proteins including ALG-2 have common features:presence of eightα-helices and dimer formation via paired EF5s that are positioned in anti-parallel orientation.ALG-2 forms a homodimer and a heterodimer with its closest paralog peflin.Like calmodulin,a well-known four-EF-hand protein,ALG-2 interacts with various proteins in a Ca2+-dependent fashion,but the binding motifs are completely different.With some exceptions,ALG-2-interacting proteins commonly contain Pro-rich regions,and ALG-2 recognizes at least two distinct Pro-containing motifs:PPYP(X) nYP(X,variable;n=4 in ALIX and PLSCR3) and PXPGF(represented by Sec31A) .A shorter alternatively spliced isoform,lacking two residues and designated ALG-2 GF122,does not bind ALIX but maintains binding capacity to Sec31A.X-ray crystal structural analyses have revealed that binding of calcium ions induces the configuration of the side chain of R125 so that it opens Pocket 1,which accepts PPYP,but Pocket 1 remains closed in the case of ALG-2 GF122.ALG-2 dimer has two ligand-binding sites,each in a monomer molecule,and appears to function as a Ca2+-dependent adaptor protein to either stabilize a preformed complex or to bridge two proteins on scaffolds in systems of the endosomal sorting complex required for transport(ESCRT) and ER-to-Golgi transport.展开更多
文摘ALG-2(a gene product of PDCD6) is a 22-kD protein containing five serially repetitive EF-hand structures and belongs to the penta-EF-hand(PEF) family,including the subunits of typical calpains.ALG-2 is the most conserved protein among the PEF family members and its homologs are widely found in eukaryotes.X-ray crystal structures of various PEF proteins including ALG-2 have common features:presence of eightα-helices and dimer formation via paired EF5s that are positioned in anti-parallel orientation.ALG-2 forms a homodimer and a heterodimer with its closest paralog peflin.Like calmodulin,a well-known four-EF-hand protein,ALG-2 interacts with various proteins in a Ca2+-dependent fashion,but the binding motifs are completely different.With some exceptions,ALG-2-interacting proteins commonly contain Pro-rich regions,and ALG-2 recognizes at least two distinct Pro-containing motifs:PPYP(X) nYP(X,variable;n=4 in ALIX and PLSCR3) and PXPGF(represented by Sec31A) .A shorter alternatively spliced isoform,lacking two residues and designated ALG-2 GF122,does not bind ALIX but maintains binding capacity to Sec31A.X-ray crystal structural analyses have revealed that binding of calcium ions induces the configuration of the side chain of R125 so that it opens Pocket 1,which accepts PPYP,but Pocket 1 remains closed in the case of ALG-2 GF122.ALG-2 dimer has two ligand-binding sites,each in a monomer molecule,and appears to function as a Ca2+-dependent adaptor protein to either stabilize a preformed complex or to bridge two proteins on scaffolds in systems of the endosomal sorting complex required for transport(ESCRT) and ER-to-Golgi transport.
