title: Exploring the molecular mechanism of stabilization of the adhesion domains of human CD2 by N-glycosylation.
abstract: N-Glycosylation is one of the most common cotranslational and post-translational modifications occurring in protein biosynthesis and plays a critical role in protein folding and structural diversification. Molecular dynamics studies of two benchmark systems, the NH(2)-terminal human CD2 adhesion domain (HsCD2ad), and the NH(2)-terminal rat CD2 adhesion domain (RnCD2ad) were carried out to investigate the energetic and dynamic effect of N-glycosylation on protein's stability. Our study revealed that N-glycosylation of HsCD2ad at the type I β-bulge turn strengthens the relevant hydrogen bonds, in particular, the hydrogen bond between Asn(65)OD1-Thr(67)HG1. Dynamic cross correlation map analysis showed that nonglycosylated HsCD2ad has strong anticorrelated motions, whereas glycosylated HsCD2ad largely destroyed this anticorrelated motion. As a result, N-glycosylation energetically and dynamically stabilizes HsCD2ad. In contrast, N-glycosylation of RnCD2ad does not display observable effect on protein's stabilization. The current theoretical result is in excellent agreement with the recent thermodynamic experiment of Culyba et al. and indicates that enthalpy and entropy may both contribute to the stabilization of human CD2 by N-glycosylation.
authors.affiliation: State Key Laboratory of Precision Spectroscopy and Department of Physics, Institute of Theoretical and Computational Science, East China Normal University, Shanghai 200062, China.
authors.forename: Xing Y
authors.initials: XY
authors.lastname: Wang
authors.forename: Chang G
authors.initials: CG
authors.lastname: Ji
authors.forename: John Z H
authors.initials: JZ
authors.lastname: Zhang
mesh_terms: D018801:CD2 Antigens / Q000737:chemistry*; D006031:Glycosylation; D006801:Humans; D006860:Hydrogen Bonding; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D055550:Protein Stability; D017434:Protein Structure, Tertiary; D013816:Thermodynamics
chemical_list: D018801:CD2 Antigens