| Autor: |
Crookston, K.P., Gonias, S.L. |
| Zdroj: |
Biochemical and Biophysical Research Communications; May 15, 1994, Vol. 200 Issue: 3 p1578-1585, 8p |
| Abstrakt: |
The reaction of α2-macroglobulin (α2M) with proteinases or methylamine causes a major conformational change in α2M and cleavage of the α2M thiol ester bonds. The resulting free Cys residues (Cys-949) contain the only free thiol groups in α2M. In this investigation, we explored the role of Cys-949 in the binding of transforming growth factor-β1 (TGF-β1) and TGF-β2 to α2M-methylamine. Modification of preformed α2M-methylamine with iodoacetamide did not change the binding affinity of α2M-methylamine for TGF-β1 or TGF-β2; the apparent KD values were 82 nM and 10 nM, respectively. TGF-β binding also remained unchanged when tested using an α2M derivative prepared by simultaneous treatment of α2M with methylamine and iodoacetamide. The slow thiol-disulfide exchange reaction that irreversibly stabilizes noncovalent growth factor-α2M-methylamine complexes was completely inhibited by modification of Cys-949. These studies demonstrate that Cys-949 in α2M is not essential for binding of TGF-β1 and TGF-β2 noncovalently; however, this residue plays a critical role in the covalent stabilization step of the reaction mechanism.Copyright 1994, 1999 Academic Press, Inc. |
| Databáze: |
Supplemental Index |
| Externí odkaz: |
|
