title: Effect of heparin on protein aggregation: inhibition versus promotion.
abstract: The effect of heparin on both native and denatured protein aggregation was investigated by turbidimetry and dynamic light scattering (DLS). Turbidimetric data show that heparin is capable of inhibiting and reversing the native aggregation of bovine serum albumin (BSA), β-lactoglobulin (BLG), and Zn-insulin at a pH near pI and at low ionic strength I; however, the results vary with regard to the range of pH, I, and protein-heparin stoichiometry required to achieve these effects. The kinetics of this process were studied to determine the mechanism by which interaction with heparin could result in inhibition or reversal of native protein aggregates. For each protein, the binding of heparin to distinctive intermediate aggregates formed at different times in the aggregation process dictates the outcome of complexation. This differential binding was explained by changes in the affinity of a given protein for heparin, partly due to the effects of protein charge anisotropy as visualized by electrostatic modeling. The heparin effect can be further extended to include inhibition of denaturing protein aggregation, as seen from the kinetics of BLG aggregation under conditions of thermally induced unfolding with and without heparin.
authors.affiliation: School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, 230027, People's Republic of China.
authors.forename: Yisheng
authors.initials: Y
authors.lastname: Xu
authors.forename: Daniel
authors.initials: D
authors.lastname: Seeman
authors.forename: Yunfeng
authors.initials: Y
authors.lastname: Yan
authors.forename: Lianhong
authors.initials: L
authors.lastname: Sun
authors.forename: Jared
authors.initials: J
authors.lastname: Post
authors.forename: Paul L
authors.initials: PL
authors.lastname: Dubin
mesh_terms: D000818:Animals; D002417:Cattle; D006493:Heparin / Q000737:chemistry / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D007328:Insulin / Q000737:chemistry; D007700:Kinetics; D007782:Lactoglobulins / Q000037:antagonists & inhibitors* / Q000737:chemistry; D017510:Protein Folding / Q000187:drug effects; D012710:Serum Albumin, Bovine / Q000037:antagonists & inhibitors* / Q000737:chemistry; D015032:Zinc / Q000737:chemistry
chemical_list: D007328:Insulin; D007782:Lactoglobulins; D012710:Serum Albumin, Bovine; D006493:Heparin; D015032:Zinc