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FFAT motif
A FFAT motif (FFAT being an acronym for two phenylalanines (FF) in an Acidic Tract ) is a protein sequence motif of six defined amino acids plus neighbouring residues that binds to the protein VAP,〔 〕 where VAP stands for VAMP-associated protein, and VAMP stands for vesicle-associated membrane protein.
==Initial definition==
The classic FFAT motif was defined on the basis of finding the sequence EFFDAxE in 16 different eukaryotic cytoplasmic proteins (where E = glutamate, F = phenylalanine, D = aspartate, A = alanine, x = any amino acid, according to the single letter amino acid code (see Table of standard amino acid abbreviations and properties in Amino Acids). In all cases, the core sequence is surrounded by regions that are rich in acids D and E (hence negatively charged), and also in residues that can acquire negative charge by phosphorylation (S and T - serine and threonine). This is the Acidic Tract of the name FFAT, and it is mainly found amino-terminal to the core motif, but also extends to the carboxy-terminal side to some extent. Also, this immediate region is almost completely devoid of basic residues (K and R - lysine and arginine).
The finding of these sequences on its own implied an important functional relationship because 13 of the 16 proteins shared the same overall function: they are lipid transfer proteins (LTPs). These include several homologs of oxysterol binding protein (OSBP, both in humans and in baker's yeast, as well as ceramide transfer protein (CERT) - previously known as Goodpasture's antigen binding protein (GPBP) or Collagen type IV alpha-3-binding protein (COL4A3BP), and Nir2/RdgB. The significance of this was enhanced by the linked finding in a proteomics study published in Nature (journal), where all three of proteins in baker's yeast with FFAT motifs (Osh1/Swh1, Osh2 and Opi1) were in protein complexes that contain Scs2, the baker's yeast homolog of VAPA and VAPB. (see Supplementary Material S1, line 375).〔http://www.nature.com/nature/journal/v415/n6868/extref/415141a-s3.pdf〕 Complexes had also been reported between OSBP and VAPA.〔 〕
This led to a simple hypothesis that VAP directly binds FFAT motifs, which was tested by biochemical interaction between purified components,〔 〕 and was later confirmed by structural analysis of VAP-FFAT complexes, both by X-ray crystallography 〔 〕 and by NMR.〔 〕 The crystallography study indicated that the parts of FFAT that interact most strongly with VAP were F2 and D4, each binding in pockets on a very electropositive, highly conserved face in the major sperm protein domain of VAP. The NMR study indicated a “fly-casting” process, whereby a weak non-specific electrostatic interaction between VAP and the acidic tract precedes the more specific high affinity interaction with EFFDAxE.
抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』
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