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FERM Domain
Class:Phospholipid binding

No Image The crystal structure of the radaxin FERM domain shows that the FERM domain consists of three subdomains that interact with one another to form a single module. Subdomain A (residues 1-82) contains one long helix and a five-stranded β-sheet. It resembles a typical ubiquitin fold; however, it has no sequence identity to this fold in other proteins and lacks a short helix between α1-β3 in the ubiquitin loop. Subdomain B (residues 96-195) is composed of four longer α-helices and one shorter helix. Subdomain B is tethered to subdomain A by a 13 residue linker helix and is classified as an acyl-coenzyme A binding protein-like fold. Subdomain C (residues 204-297) consists of a seven-stranded β-sandwich core and a single α-helix. Subdomain C is tethered to subdomain B by an eight-residue linker and is structurally similar to the PTB domain.
Structure Reference:

Hamada, K. et al. (2000) EMBO J. 19(17): 4449-4462. PDB: 1GC6.

Domain binding and function:
Previously known as the B4.1 (band 4.1) homology and ERM domain, the FERM domain is named for the four proteins in which this domain was originally described: F for Band 4.1, E for Ezrin, R for Radixin, M for Moesin. The FERM domain is approximately 300 amino acids in length and is found in a number of cytoskeletal-associated proteins that are found at the interface between the plasma membrane and the cytoskeleton. The FERM domain is responsible for PIP2 regulated membrane binding of ERM (Ezrin/Radixin/Moesin) proteins that play a role in formation of membrane-associated cytoskeleton by linking actin filaments to adhesion proteins. Merlin, a FERM domain containing adaptor protein has been shown to act as a tumour suppressor. FERM domains contain three lobes with the most N-terminal lobe resembling ubiquitin, the central lobe resembling acyl-CoA binding proteins and the most C-terminal lobe having a related structure to PTB domains. The structure of the Radixin FERM domain bound to IP3 has been solved and, surprisingly, phosphoinositide binding is not mediated by the PH-fold subdomain of FERM, but occurs at a cleft between two subdomains on a relatively flat face of the module. The FERM domain is also postulated to bind to adhesion proteins, in a PIP2 -regulated fashion, providing a link between cytoskeletal signals and membrane dynamics.
Examples of Proteins: 
FERM domain protein
Binding partner

integrin β subunits2
Radixin IP3, PI(4,5)P2
ERM PI(4,5)P2

PI(3)P, PI(4)P, PI(5)P

PI(3)P, PI(4)P, PI(5)P



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