title: The core trisaccharide of an N-linked glycoprotein intrinsically accelerates folding and enhances stability.
abstract: The folding energetics of the mono-N-glycosylated adhesion domain of the human immune cell receptor cluster of differentiation 2 (hCD2ad) were studied systematically to understand the influence of the N-glycan on the folding energy landscape. Fully elaborated N-glycan structures accelerate folding by 4-fold and stabilize the beta-sandwich structure by 3.1 kcal/mol, relative to the nonglycosylated protein. The N-glycan's first saccharide unit accounts for the entire acceleration of folding and for 2/3 of the native state stabilization. The remaining third of the stabilization is derived from the next 2 saccharide units. Thus, the conserved N-linked triose core, ManGlcNAc(2), improves both the kinetics and the thermodynamics of protein folding. The native state stabilization and decreased activation barrier for folding conferred by N-glycosylation provide a powerful and potentially general mechanism for enhancing folding in the secretory pathway.
authors.affiliation: Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Sarah R
authors.initials: SR
authors.lastname: Hanson
authors.forename: Elizabeth K
authors.initials: EK
authors.lastname: Culyba
authors.forename: Tsui-Ling
authors.initials: TL
authors.lastname: Hsu
authors.forename: Chi-Huey
authors.initials: CH
authors.lastname: Wong
authors.forename: Jeffery W
authors.initials: JW
authors.lastname: Kelly
authors.forename: Evan T
authors.initials: ET
authors.lastname: Powers
mesh_terms: D000818:Animals; D018801:CD2 Antigens / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D002942:Circular Dichroism; D006023:Glycoproteins / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008958:Models, Molecular; D009154:Mutation / Q000235:genetics; D017510:Protein Folding; D055550:Protein Stability; D017434:Protein Structure, Tertiary; D051381:Rats; D014312:Trisaccharides / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D018801:CD2 Antigens; D006023:Glycoproteins; D014312:Trisaccharides