Endocrinology, Vol 135, 768-773, Copyright © 1994 by Endocrine Society

ARTICLES

Corticotropin-releasing factor binding protein dimerizes after association with ligand

RJ Woods, KM Kennedy, JM Gibbins, D Behan, W Vale and PJ Lowry
Department of Biochemistry and Physiology, University of Reading, Whiteknights, Berks, United Kingdom.

We have suggested recently that the fall in plasma CRF-binding protein (BP) during the last few weeks of pregnancy is a direct effect of association with its ligand because of the rapid decrease in plasma BP concentration seen in normal males reaching a nadir some 15 min after a bolus injection of synthetic CRF. In the present study, we have investigated the physicochemical properties of both natural and recombinant BP by gel filtration under physiological conditions and have shown that association of human CRF to this BP results in an increase in molecular weight consistent with the formation of a dimer form of the BP ligand complex. The dimer is more stable when the interaction occurs in the presence of serum or if a peptide with a higher affinity for the BP is substituted as ligand. Experimental evidence would also suggest that the dimer BP has a higher affinity for ligand than the monomeric form. We suggest that this dimerization occurs in vivo when CRF is released into the bloodstream and provides the trigger that causes the uptake of the complex at specific receptor sites.

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