5ftl: Difference between revisions
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== Function == | == Function == | ||
[[http://www.uniprot.org/uniprot/TERA_HUMAN TERA_HUMAN]] Necessary for the fragmentation of Golgi stacks during mitosis and for their reassembly after mitosis. Involved in the formation of the transitional endoplasmic reticulum (tER). The transfer of membranes from the endoplasmic reticulum to the Golgi apparatus occurs via 50-70 nm transition vesicles which derive from part-rough, part-smooth transitional elements of the endoplasmic reticulum (tER). Vesicle budding from the tER is an ATP-dependent process. The ternary complex containing UFD1L, VCP and NPLOC4 binds ubiquitinated proteins and is necessary for the export of misfolded proteins from the ER to the cytoplasm, where they are degraded by the proteasome. The NPLOC4-UFD1L-VCP complex regulates spindle disassembly at the end of mitosis and is necessary for the formation of a closed nuclear envelope. Regulates E3 ubiquitin-protein ligase activity of RNF19A (By similarity). Component of the VCP/p97-AMFR/gp78 complex that participates in the final step of the sterol-mediated ubiquitination and endoplasmic reticulum-associated degradation (ERAD) of HMGCR. Also involved in DNA damage response: recruited to double-strand breaks (DSBs) sites in a RNF8- and RNF168-dependent manner and promotes the recruitment of TP53BP1 at DNA damage sites. Recruited to stalled replication forks by SPRTN: may act by mediating extraction of DNA polymerase eta (POLH) to prevent excessive translesion DNA synthesis and limit the incidence of mutations induced by DNA damage.<ref>PMID:15456787</ref> <ref>PMID:16168377</ref> <ref>PMID:22020440</ref> <ref>PMID:22120668</ref> <ref>PMID:22607976</ref> <ref>PMID:23042607</ref> <ref>PMID:23042605</ref> | [[http://www.uniprot.org/uniprot/TERA_HUMAN TERA_HUMAN]] Necessary for the fragmentation of Golgi stacks during mitosis and for their reassembly after mitosis. Involved in the formation of the transitional endoplasmic reticulum (tER). The transfer of membranes from the endoplasmic reticulum to the Golgi apparatus occurs via 50-70 nm transition vesicles which derive from part-rough, part-smooth transitional elements of the endoplasmic reticulum (tER). Vesicle budding from the tER is an ATP-dependent process. The ternary complex containing UFD1L, VCP and NPLOC4 binds ubiquitinated proteins and is necessary for the export of misfolded proteins from the ER to the cytoplasm, where they are degraded by the proteasome. The NPLOC4-UFD1L-VCP complex regulates spindle disassembly at the end of mitosis and is necessary for the formation of a closed nuclear envelope. Regulates E3 ubiquitin-protein ligase activity of RNF19A (By similarity). Component of the VCP/p97-AMFR/gp78 complex that participates in the final step of the sterol-mediated ubiquitination and endoplasmic reticulum-associated degradation (ERAD) of HMGCR. Also involved in DNA damage response: recruited to double-strand breaks (DSBs) sites in a RNF8- and RNF168-dependent manner and promotes the recruitment of TP53BP1 at DNA damage sites. Recruited to stalled replication forks by SPRTN: may act by mediating extraction of DNA polymerase eta (POLH) to prevent excessive translesion DNA synthesis and limit the incidence of mutations induced by DNA damage.<ref>PMID:15456787</ref> <ref>PMID:16168377</ref> <ref>PMID:22020440</ref> <ref>PMID:22120668</ref> <ref>PMID:22607976</ref> <ref>PMID:23042607</ref> <ref>PMID:23042605</ref> | ||
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== Publication Abstract from PubMed == | |||
p97 is a hexameric AAA ATPase that is an attractive target for cancer drug development. Here, we report cryo-EM structures for ADP-bound, full-length, hexameric wild-type p97 in the presence and absence of an allosteric inhibitor at resolutions of 2.3 A and 2.4 A, respectively. We also report cryo-EM structures at ~ 3.3 A, 3.2 A and 3.3 A resolutions respectively, for three distinct, co-existing functional states of p97 with occupancies of 0, 1 or 2 molecules of ATPgammaS per protomer. A large corkscrew-like change in molecular architecture coupled with upward displacement of the N-domain is observed only when ATPgammaS is bound to both D1 and D2 domains. These cryo-EM structures establish the sequence of nucleotide-driven structural changes in p97 at atomic resolution. They also enable elucidation of the binding mode of an allosteric small molecule inhibitor to p97 and illustrate how inhibitor binding at the interface between D1 and D2 domains prevents propagation of the conformational changes necessary for p97 function. | |||
2.3 A resolution cryo-EM structure of human p97 and mechanism of allosteric inhibition.,Banerjee S, Bartesaghi A, Merk A, Rao P, Bulfer SL, Yan Y, Green N, Mroczkowski B, Neitz RJ, Wipf P, Falconieri V, Deshaies RJ, Milne JL, Huryn D, Arkin M, Subramaniam S Science. 2016 Jan 28. pii: aad7974. PMID:26822609<ref>PMID:26822609</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
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== References == | == References == | ||
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