alpha-Hemoglobin Stabilizing Protein (AHSP), a Kinetic Scheme of the Action of a Human Mutant, AHSP(V56G)

作者：Brillet Thomas; Baudin Creuza Veronique; Vasseur Corinne; Domingues Hamdi Elisa; Kiger Laurent; Wajcman Henri; Pissard Serge; Marden Michael C^*

来源：JOURNAL OF BIOLOGICAL CHEMISTRY, 2010, 285(23): 17986-17992.

DOI：10.1074/jbc.M109.098491

A kinetic analysis has been made of the interaction of alpha-Hb chains with a mutant alpha-hemoglobin stabilizing protein, AHSP(V56G), which is the first case of an AHSP mutation associated with clinical symptoms of mild thalassemia syndrome. The chaperone AHSP is thought to protect nascent alpha chains until final binding to the partner beta-Hb. Rather than protecting alpha chains, the mutant chaperone is partially unfolded but recovers its secondary structure via interaction with alpha-Hb. For both AHSP(WT) and AHSP(V56G), the binding to alpha-Hb is quite rapid relative to the alpha-beta reaction, as expected because the chaperone binding must be quite competitive to complete the alpha chain folding process before alpha-Hb binds irreversibly to beta-Hb. The main kinetic difference is a dissociation rate of AHSP(V56G).alpha-Hb some four times faster relative to AHSP.alpha-Hb. Considering a role of protein folding, the AHSPV56G apparently does not bind long enough (0.5 s versus 2 s for the WT) to complete the structural modifications. The overall replacement reaction (AHSP.alpha-Hb + beta-Hb -> AHSP + alpha beta) can be quite long, especially if there is an excess of AHSP relative to beta-Hb monomers.

• 出版日期2010-6-4