Acyl coenzyme A binding protein. Conformational sensitivity to long chain fatty acyl-CoA.
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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.
