title: Acyl coenzyme A binding protein. Conformational sensitivity to long chain fatty acyl-CoA.
abstract: Cellular unbound long chain fatty acyl-CoAs (>14 carbon) are potent regulators of gene transcription and intracellular signaling. Although the cytosolic acyl-CoA binding protein (ACBP) has high affinity for medium chain fatty acyl-CoAs, direct interaction of ACBP with >14-carbon fatty acyl-CoAs has not been established. Steady state, photon counting fluorescence spectroscopy directly established that rat liver ACBP bound 18-carbon cis- and trans-parinaroyl-CoA, Kd = 7.03 +/- 0.95 and 4.40 +/- 0.43 nM. Time-resolved fluorometry revealed that ACBP-bound parinaroyl-CoAs had high rotational freedom within the single, relatively hydrophobic (epsilon <32), binding site. Tyr and Trp fluorescence dynamics demonstrated that apo-ACBP was an ellipsoidal protein (axes of 15 and 9 A) whose conformation was altered by oleoyl-CoA in the holo-ACBP as shown by a 2-A decrease of ACBP hydrodynamic diameter and increased Trp segmental motions. Thus, native liver ACBP binds >14-carbon fatty acyl-CoAs with nanomolar affinity at a single binding site. Acyl-CoA-induced conformational alterations in ACBP may be significant to its putative functions in lipid metabolism and regulation of processes sensitive to unbound long chain fatty acyl-CoAs.
authors.affiliation: Department of Physiology and Pharmacology, Texas A & M University, TVMC, College Station, Texas 77843-4466, USA.
authors.forename: A
authors.initials: A
authors.lastname: Frolov
authors.forename: F
authors.initials: F
authors.lastname: Schroeder
mesh_terms: D000214:Acyl Coenzyme A / Q000378:metabolism*; D000818:Animals; D008099:Liver / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism; D051381:Rats; D013050:Spectrometry, Fluorescence
chemical_list: D000214:Acyl Coenzyme A; D011506:Proteins; C017585:oleoyl-coenzyme A