Molecular aspects of fatty acid transport: mutations in the IYTSGTTGXPK motif impair fatty acid transport protein function.
The murine fatty acid transport protein (FATP) facilitates uptake of long chain fatty acids (LCFAs) when expressed in mammalian cells. FATP's sequence contains a highly conserved motif, IYTSGTTGXPK, also found in a number of proteins known to interact with ATP. To explore the role of this motif, we independently mutated the central serine (serine 250) and threonine (threonine 252) residues in this motif and assessed the effects of these mutations on FATP function. When expressed in fibroblasts, the FATP mutants demonstrated impaired LCFA import and impaired binding of [alpha-32P]8-azido-ATP (azido-ATP) compared with wild-type FATP. These results suggest that serine 250 and threonine 252 are critical for FATP function and that the mechanism of action of FATP involves nucleotide binding which is dependent on these residues.
Stuhlsatz-Krouper
S M
SM
Center for Cardiovascular Research, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO 63110-1010, USA.
Bennett
N E
NE
Schaffer
J E
JE
D016475:3T3 Cells; D000409:Alanine / Q000235:genetics; D020816:Amino Acid Motifs; D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D002460:Cell Line; D050612:Fatty Acid Transport Proteins; D005227:Fatty Acids / Q000378:metabolism*; D005998:Glycine / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D026901:Membrane Transport Proteins; D051379:Mice; D016297:Mutagenesis, Site-Directed; D017354:Point Mutation; D012694:Serine / Q000235:genetics; D013912:Threonine / Q000235:genetics
D002352:Carrier Proteins; D050612:Fatty Acid Transport Proteins; D005227:Fatty Acids; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C493572:Slc27a4 protein, mouse; D013912:Threonine; D012694:Serine; D000409:Alanine; D005998:Glycine