Biology:IMD domain

From HandWiki
IRSp53/MIM homology domain
PDB 1wdz EBI.jpg
crystal structure of rcb domain of irsp53
Identifiers
SymbolIMD
PfamPF08397
Pfam clanCL0145
InterProIPR013606

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. 1.0 1.1 "A novel actin bundling/filopodium-forming domain conserved in insulin receptor tyrosine kinase substrate p53 and missing in metastasis protein". J. Biol. Chem. 279 (15): 14929–36. April 2004. doi:10.1074/jbc.M309408200. PMID 14752106. 
  2. "Characterisation of IRTKS, a novel IRSp53/MIM family actin regulator with distinct filament bundling properties". J. Cell Sci. 120 (Pt 9): 1663–72. May 2007. doi:10.1242/jcs.001776. PMID 17430976. 
  3. 3.0 3.1 "Structural basis of filopodia formation induced by the IRSp53/MIM homology domain of human IRSp53". EMBO J. 24 (2): 240–50. January 2005. doi:10.1038/sj.emboj.7600535. PMID 15635447. 
  4. "Extracellular fragment of brain-specific angiogenesis inhibitor 1 suppresses endothelial cell proliferation by blocking alphavbeta5 integrin". Exp. Cell Res. 294 (1): 172–84. March 2004. doi:10.1016/j.yexcr.2003.11.008. PMID 14980512. 
  5. "MIM: a multifunctional scaffold protein". J. Mol. Med. 85 (6): 569–76. June 2007. doi:10.1007/s00109-007-0207-0. PMID 17497115. 
  6. "Structural basis for the actin-binding function of missing-in-metastasis". Structure 15 (2): 145–55. February 2007. doi:10.1016/j.str.2006.12.005. PMID 17292833. 
This article incorporates text from the public domain Pfam and InterPro: IPR013606