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
Dear Editor To date,tens of millions of people have been infected with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),causing the outbreak of the respiratory disease named the coronavirus disease 2019(COV...Dear Editor To date,tens of millions of people have been infected with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),causing the outbreak of the respiratory disease named the coronavirus disease 2019(COVID-19).As a newly emerged member of the coronavirus family,SARS-CoV-2 is an enveloped positive-strand RNA virus,which has probably the largest genome(approximately 30 kb)among all RNA viruses.The nucleocapsid(N)protein of SARS-CoV-2 is mainly responsible for recognizing and wrapping viral RNA into helically symmetric structures(Malik,2020).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.
基金This work was supported in part by the National Natural Science Foundation of China(61872216 and 81630103 to JZ,31900862 to DZ,31871443 to PL)the National Key R&D Program(2019YFA0508403 to PL,2020YFA0803300 to HL)the Turing Al Institute of Nanjing and the Zhongguancun Haihua Institute for Frontier Information Technology.
文摘Dear Editor To date,tens of millions of people have been infected with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),causing the outbreak of the respiratory disease named the coronavirus disease 2019(COVID-19).As a newly emerged member of the coronavirus family,SARS-CoV-2 is an enveloped positive-strand RNA virus,which has probably the largest genome(approximately 30 kb)among all RNA viruses.The nucleocapsid(N)protein of SARS-CoV-2 is mainly responsible for recognizing and wrapping viral RNA into helically symmetric structures(Malik,2020).
