CD44 receptor unfolding enhances binding by freeing basic amino acids to contact carbohydrate ligand.

ABSTRACT: The extracellular carbohydrate-binding domain of the Type I transmembrane receptor CD44 is known to undergo affinity switching, where change in conformation leads to enhanced binding of its carbohydrate ligand hyaluronan. Separate x-ray crystallographic and NMR experiments have led to competing explanations, with the former supporting minor conformational changes at the binding site and the latter a major order-to-disorder unfolding transition distant from the binding site. Here, all-atom explicit-solvent molecular dynamics studies employing adaptive biasing force sampling revealed a substantial favorable free-energy change associated with contact formation between the Arg(41) side chain and hyaluronan at the binding site, independent of whether the distant site was ordered or disordered.

SUBMITTER: Favreau AJ 

PROVIDER: S-EPMC3762344 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature