// Workers AI · dad joke modeWhy was the IMD domain sad? It had a lot of "site" issues.
| IRSp53/MIM homology domain | |||||||
|---|---|---|---|---|---|---|---|
 crystal structure of rcb domain of irsp53 | |||||||
| Identifiers | |||||||
| Symbol | IMD | ||||||
| Pfam | PF08397 | ||||||
| Pfam clan | CL0145 | ||||||
| InterPro | IPR013606 | ||||||
| |||||||
In molecular biology, the IMD domain (IRSp53 and MIM (missing in metastases) homology Domain) or I-BAR domain (Inverse BAR 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[1][2][3]. Filopodium-inducing IMD activity is regulated by Cdc42 and Rac1 (Rho-family GTPases) and is SH3-independent, and dependent on the membrane binding and deforming activity.[4][5]
Family members
[edit]The IRSp53/MIM family is a membrane deforming and novel F-actin bundling protein family that includes invertebrate relatives:
- Vertebrate MIM (missing in metastasis) (MTSS1), an actin-binding scaffold protein that may be involved in cancer metastasis.
- Vertebrate ABBA-1 (MTSS1L), a MIM-related protein.
- Vertebrate brain-specific angiogenesis inhibitor 1-associated protein 2 (BAI1-associated protein 2) or insulin receptor tyrosine kinase substrate p53 (IRSp53), a multifunctional adaptor protein that links Rac1 with a Wiskott–Aldrich syndrome family verprolin-homologous protein 2 (WAVE2/WASF2) to induce lamellipodia or Cdc42 with Mena to induce filopodia.[6]
- Vertebrate brain-specific angiogenesis inhibitor 1-associated protein 2-like proteins 1 and 2 (BAI1-associated protein 2-like proteins 1 and 2, BAIAP2L1 and BAIAP2L2).
- Drosophila melanogaster (Fruit fly) CG32082-PA.
- Caenorhabditis elegans M04F3.5 protein.
Subgroups
[edit]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][7][8]
Structure
[edit]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.[4] 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 that is compatible for plasma membrane protrusions including filopodia and spines.[4][5] 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.[9][5] The WH2 domain performs a scaffolding function.[10]
References
[edit]- 1 2 Yamagishi A, Masuda M, Ohki T, Onishi H, Mochizuki N (April 2004). "A novel actin bundling/filopodium-forming domain conserved in insulin receptor tyrosine kinase substrate p53 and missing in metastasis protein". The Journal of Biological Chemistry. 279 (15): 14929–14936. doi:10.1074/jbc.M309408200. PMID 14752106.
- ↑ Millard TH, Dawson J, Machesky LM (May 2007). "Characterisation of IRTKS, a novel IRSp53/MIM family actin regulator with distinct filament bundling properties". Journal of Cell Science. 120 (Pt 9): 1663–1672. doi:10.1242/jcs.001776. PMID 17430976. S2CID 39973979.
- ↑ Millard TH, Bompard G, Heung MY, Dafforn TR, Scott DJ, Machesky LM, et al. (January 2005). "Structural basis of filopodia formation induced by the IRSp53/MIM homology domain of human IRSp53". The EMBO Journal. 24 (2): 240–250. doi:10.1038/sj.emboj.7600535. PMC 545821. PMID 15635447.
- 1 2 3 Suetsugu S, Murayama K, Sakamoto A, Hanawa-Suetsugu K, Seto A, Oikawa T, et al. (November 2006). "The RAC binding domain/IRSp53-MIM homology domain of IRSp53 induces RAC-dependent membrane deformation". The Journal of Biological Chemistry. 281 (46) (published 2006): 35347–35358. doi:10.1074/jbc.M606814200. PMID 17003044.
- 1 2 3 Mattila PK, Pykäläinen A, Saarikangas J, Paavilainen VO, Vihinen H, Jokitalo E, et al. (March 2007). "Missing-in-metastasis and IRSp53 deform PI(4,5)P2-rich membranes by an inverse BAR domain-like mechanism". The Journal of Cell Biology. 176 (7): 953–964. doi:10.1083/jcb.200609176. PMC 2064081. PMID 17371834.
- ↑ Koh JT, Kook H, Kee HJ, Seo YW, Jeong BC, Lee JH, et al. (March 2004). "Extracellular fragment of brain-specific angiogenesis inhibitor 1 suppresses endothelial cell proliferation by blocking alphavbeta5 integrin". Experimental Cell Research. 294 (1): 172–184. doi:10.1016/j.yexcr.2003.11.008. PMID 14980512.
- ↑ Machesky LM, Johnston SA (June 2007). "MIM: a multifunctional scaffold protein". Journal of Molecular Medicine. 85 (6). Berlin, Germany: 569–576. doi:10.1007/s00109-007-0207-0. PMID 17497115. S2CID 32096007.
- ↑ Miki H, Yamaguchi H, Suetsugu S, Takenawa T (December 2000). "IRSp53 is an essential intermediate between Rac and WAVE in the regulation of membrane ruffling". Nature. 408 (6813): 732–735. doi:10.1038/35047107. PMID 11130076.
- ↑ Scita G, Confalonieri S, Lappalainen P, Suetsugu S (February 2008). "IRSp53: crossing the road of membrane and actin dynamics in the formation of membrane protrusions". Trends in Cell Biology. 18 (2): 52–60. doi:10.1016/j.tcb.2007.12.002. PMID 18215522.
- ↑ Lee SH, Kerff F, Chereau D, Ferron F, Klug A, Dominguez R (February 2007). "Structural basis for the actin-binding function of missing-in-metastasis". Structure. 15 (2). London: 145–155. doi:10.1016/j.str.2006.12.005. PMC 1853380. PMID 17292833.