Molecular Recognition in Pathological Crystallizations: Gout. Interactions between Albumin and Sodium Urate Mono-hydrate Crystals

Abstract Pathological crystallizations encompass a range of diseases caused by the formation of unwanted crystals in the body fluids. We investigate the relations between these crystals and proteins present in the biological environment, aiming at a basic understanding of their interactions at a molecular level. We focused on the crystallization of monosodium urate monohydrate (MSU), related to the disease of gout. Human serum albumin (HSA), which is found associated with the crystals in gouty patients, acts in vitro as a crystal nucleator of MSU. Morphological and immunolabeling studies showed a selective Interaction of HSA with the {110} faces of MSU crystals. These faces are formed of homocharged layers of sodium cations or urate anions. The nucleating effect is pH dependent, with the mid-point of the curve around physiological pH. Blocking reactions Indicate that carboxylate groups are active in the nucleation of MSU. We propose a nucleation mechanism whereby structured anionic domains on the protein ...