Abstract 2050 Serum albumin binds stoichiometrically to the insulin-resistance protein Fetuin-A with high affinity

The alpha-2-HS-glycoprotein, (AHSG, or Fetuin-A), is a protein of strong interest in diabetes research, having been implicated in the pathogenesis of insulin resistance. Physiological functions of the hepatokine, Fetuin-A, include roles in endocytosis, brain development, and formation of bone tissue. Fetuin-A is also an established inhibitor of the insulin receptor tyrosine kinase activity. Some studies have alluded to a potential interaction between Fetuin-A and albumin. A physiological interaction between these two plasma proteins presents a novel dimension to research in regulation of blood glucose level and its disorders, such as type 2 diabetes. In this study, we used pull-down assays and spectroscopic analysis to provide the first experimental evidence indicating a direct physical interaction between Fetuin-A and serum albumin. Surface plasmon resonance kinetic studies revealed a high binding affinity with a KD of 1.3 x 10-9 M and a binding ratio (Fetuin-A to serum albumin) of 1:2. Ongoing studies include further characterization using computation, liquid chromatography, and pull-down from plasma. The study was partially funded by an ASBMB Undergraduate Research Award, a SURE award from SFA College of Sciences and Mathematics, and a Welch Foundation Departmental Grant (AN-0008).