IMD domain

In molecular biology, the IMD domain is a BAR-like domain of approximately 250 amino acids found at the N-terminus in the insulin receptor tyrosine kinase substrate p53 and in the evolutionarily related IRSp53/MIM 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 and is SH3-independent. The IRSp53/MIM family is a novel F-actin bundling protein family that includes invertebrate relatives:

Vertebrate MIM, an actin-binding scaffold protein that may be involved in cancer metastasis.
Vertebrate ABBA-1, a MIM-related protein.
Vertebrate brain-specific angiogenesis inhibitor 1-associated protein 2 or insulin receptor tyrosine kinase substrate p53, a multifunctional adaptor protein that links Rac1 with a Wiskott–Aldrich syndrome family verprolin-homologous protein 2 to induce lamellipodia or Cdc42 with Mena to induce filopodia.
Vertebrate brain-specific angiogenesis inhibitor 1-associated protein 2-like proteins 1 and 2.Drosophila melanogaster CG32082-PA.Caenorhabditis elegans M04F3.5 protein.

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.
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 domain, a functional module serving both as a sensor and inducer of membrane curvature. 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.