title: Single amino acid substitutions in the C-terminus of collagen II alter its affinity for collagen IX.
abstract: The structural integrity of cartilage depends on the presence of extracellular matrices (ECM) formed by heterotypic fibrils composed of collagen II, collagen IX, and collagen XI. The formation of these fibrils depends on the site-specific binding between relatively small regions of interacting collagen molecules. Single amino acid substitutions in collagen II change the physicochemical and structural characteristics of those sites, thereby leading to an alteration of intermolecular collagen II/collagen IX interaction. Employing a biosensor to study interactions between R75C, R789C or G853E collagen II mutants and collagen IX, we demonstrated significant changes in the binding affinities. Moreover, analyses of computer models representing mutation sites defined exact changes in physicochemical characteristics of collagen II mutants. Our study shows that changes in collagen II/collagen IX affinity could represent one of the steps in a cascade of changes occurring in the ECM of cartilage as a result of single amino acid substitutions in collagen II.
authors.affiliation: Department of Dermatology and Cutaneous Biology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USA.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Steplewski
authors.forename: Raymond
authors.initials: R
authors.lastname: Brittingham
authors.forename: Sergio A
authors.initials: SA
authors.lastname: Jimenez
authors.forename: Andrzej
authors.initials: A
authors.lastname: Fertala
mesh_terms: D019943:Amino Acid Substitution; D024043:Collagen Type II / Q000737:chemistry / Q000378:metabolism*; D024081:Collagen Type IX / Q000378:metabolism*; D003198:Computer Simulation; D008958:Models, Molecular; D011485:Protein Binding; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D055672:Static Electricity
chemical_list: D024043:Collagen Type II; D024081:Collagen Type IX; D011994:Recombinant Proteins