“IMD domain”的意思、由来-开放百科全书

In molecular biology, the IMD domain (IRSp53 and MIM (missing in metastases) homology Domain) is a BAR-like domain of approximately 250 amino acids found at the N-terminus in the insulin receptor tyrosine kinase substrate p53 (IRSp53/BAIAP2) and in the evolutionarily related IRSp53/MIM (MTSS1) family. In IRSp53, a ubiquitous regulator of the actin cytoskeleton, the IMD domain acts as conserved F-actin bundling domain involved in filopodium formation. Filopodium-inducing IMD activity is regulated by Cdc42 and Rac1 (Rho-family GTPases) and is SH3-independent.^[1]^[2]^[3] The IRSp53/MIM family is a novel F-actin bundling protein family that includes invertebrate relatives:

The vertebrate IRSp53/MIM family is divided into two major groups: the IRSp53 subfamily and the MIM/ABBA subfamily. The putative invertebrate homologues are positioned between them. The IRSp53 subfamily members contain an SH3 domain, and the MIM/ABBA subfamily proteins contain a WH2 (WASP-homology 2) domain. The vertebrate SH3-containing subfamily is further divided into three groups according to the presence or absence of the WWB and the half-CRIB motif. The IMD domain can bind to and bundle actin filaments, bind to membranes and interact with the small GTPase Rac.^[1]^[5]

The IMD domain folds as a coiled coil of three extended alpha-helices and a shorter C-terminal helix. Helix 4 packs tightly against the other three helices, and thus represents an integral part of the domain. The fold of the IMD domain closely resembles that of the BAR (Bin-Amphiphysin-RVS) domain, a functional module serving both as a sensor and inducer of membrane curvature.^[3] The IMD domain is also known as the I-BAR domain because of its inverse curvature of the membrane binding surface compared to that of the BAR domain. The WH2 domain performs a scaffolding function.^[6]

References

1. ^¹{{cite journal |vauthors=Yamagishi A, Masuda M, Ohki T, Onishi H, Mochizuki N | title = A novel actin bundling/filopodium-forming domain conserved in insulin receptor tyrosine kinase substrate p53 and missing in metastasis protein | journal = J. Biol. Chem. | volume = 279 | issue = 15 | pages = 14929–36 |date=April 2004 | pmid = 14752106 | doi = 10.1074/jbc.M309408200 | url = }}
2. ^{{cite journal |vauthors=Millard TH, Dawson J, Machesky LM | title = Characterisation of IRTKS, a novel IRSp53/MIM family actin regulator with distinct filament bundling properties | journal = J. Cell Sci. | volume = 120 | issue = Pt 9 | pages = 1663–72 |date=May 2007 | pmid = 17430976 | doi = 10.1242/jcs.001776 | url = }}
3. ^¹{{cite journal |vauthors=Millard TH, Bompard G, Heung MY, Dafforn TR, Scott DJ, Machesky LM, Fütterer K | title = Structural basis of filopodia formation induced by the IRSp53/MIM homology domain of human IRSp53 | journal = EMBO J. | volume = 24 | issue = 2 | pages = 240–50 |date=January 2005 | pmid = 15635447 | pmc = 545821 | doi = 10.1038/sj.emboj.7600535 | url = }}
4. ^{{cite journal |vauthors=Koh JT, Kook H, Kee HJ, Seo YW, Jeong BC, Lee JH, Kim MY, Yoon KC, Jung S, Kim KK | title = Extracellular fragment of brain-specific angiogenesis inhibitor 1 suppresses endothelial cell proliferation by blocking alphavbeta5 integrin | journal = Exp. Cell Res. | volume = 294 | issue = 1 | pages = 172–84 |date=March 2004 | pmid = 14980512 | doi = 10.1016/j.yexcr.2003.11.008 | url = }}
5. ^{{cite journal |vauthors=Machesky LM, Johnston SA | title = MIM: a multifunctional scaffold protein | journal = J. Mol. Med. | volume = 85 | issue = 6 | pages = 569–76 |date=June 2007 | pmid = 17497115 | doi = 10.1007/s00109-007-0207-0 | url = }}
6. ^{{cite journal |vauthors=Lee SH, Kerff F, Chereau D, Ferron F, Klug A, Dominguez R | title = Structural basis for the actin-binding function of missing-in-metastasis | journal = Structure | volume = 15 | issue = 2 | pages = 145–55 |date=February 2007 | pmid = 17292833 | pmc = 1853380 | doi = 10.1016/j.str.2006.12.005 | url = }}