Collagen Type XI α1 Chain Amino Propeptide Structural Model and Glycosaminoglycan Interactions in Silico
Modeling of the collagen α1(XI) amino propeptide (NPP) domain was performed to better understand how dimerization and glycosaminoglycan binding are coordinated. The program MODELLER was used to generate a homology model of collagen α1(XI) NPP domain based on the crystal structure of the closely related NC4 domain of collagen α1 (IX) (PDB:2UUR) to a root mean square deviation (rmsd) of 0.785 Å resolution. A model of collagen α1(XI) NPP domain dimer was constructed in two alternative templates; 1) the thrombospondin dimer template (PDB:1Z78), and 2) by submission of two monomer subunits based on PDB:2UUR to ClusPro. Calculation of relative binding energy for the interaction between each collagen α1(XI) NPP model and glycosaminoglycans as ligands was performed using AutoDock4. Results support a higher affinity between heparan sulfate and the dimer compared to the monomer. Sequential point mutation studies in the putative binding site (147-KKKITK-152) indicated the importance of each basic lysine residue in the binding of heparan sulfate. Two orders of magnitude change in binding affinity was predicted when comparing wild type to the mutation K152A.
Mallory, Christopher; McDougal, Owen; and Oxford, Julia. (2011). "Collagen Type XI α1 Chain Amino Propeptide Structural Model and Glycosaminoglycan Interactions in Silico". International Conference of Bioinformatics and Computational Biology Proceedings, 632-635.