InterPro domain: IPR028565

The mu homology domain (MHD) is an ~280 residue protein-protein interactionmodule, which is found in endocytotic proteins involved in clathrin-mediatedendocytosis [ 1 , 2 , 3 , 4 ]:

• Mu subunits of adaptor protein (AP) complexes, AP-1, AP-2, AP-3, and AP-4.
• Proteins of the stonin family.
• Proteins of the muniscin family: Syp1, FCHO1/2 and SGIP1.

The MHD domain has an elongated, banana-shaped, all beta-sheet structure. It can be considered as two beta-sandwich subdomains (A and B), with subdomain B inserted between strands 6 and 15 of subdomain A, and joined edge to edge such that the convex surface is a continuous nine-stranded mixedbeta-sheet that runs the whole length of the molecule. The tyrosine based signal binds to a site on the surface of two parallel beta-sheet strands (beta1 and beta16) in subdomain A [ 5 , 5 ].

1. Stonin 2: an adaptor-like protein that interacts with components of the endocytic machinery. J. Cell Biol. 153, 1111-20
2. Human stoned B interacts with AP-2 and synaptotagmin and facilitates clathrin-coated vesicle uncoating. EMBO Rep. 2, 634-40
3. Functional dissection of the interactions of stonin 2 with the adaptor complex AP-2 and synaptotagmin. Proc. Natl. Acad. Sci. U.S.A. 101, 964-9
4. Syp1 is a conserved endocytic adaptor that contains domains involved in cargo selection and membrane tubulation. EMBO J. 28, 3103-16
5. A structural explanation for the recognition of tyrosine-based endocytotic signals. Science 282, 1327-32