Design of Glyco-Linkers at Multiple Structural Levels to Modulate Protein Stability
Autor: | Changling Zou, Chun Li, Xiaoyan Wang, Lina Zhao, Yuhui Hou, Xudong Feng, Beijia Han |
---|---|
Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
Glycosylation Aspergillus oryzae Molecular Dynamics Simulation 010402 general chemistry 01 natural sciences Pichia 03 medical and health sciences chemistry.chemical_compound Protein stability N-linked glycosylation Polysaccharides General Materials Science Physical and Theoretical Chemistry Cellulose Thermostability Glucuronidase Glycoproteins chemistry.chemical_classification Protein Stability Carbohydrate 0104 chemical sciences 030104 developmental biology Enzyme Biochemistry chemistry Mutation |
Zdroj: | The journal of physical chemistry letters. 9(16) |
ISSN: | 1948-7185 |
Popis: | N-glycosylation has critical roles in regulating protein stability, but the molecular basis is poorly understood. In this study, we integrated experimental and computational techniques to investigate the mechanism by which full-length N-glycans modulate protein stability from quaternary structure perspective. We found the two inherent N-glycans of β-glucuronidase expressed in Pichia pastoris function as "glyco-linkers" that hold spatially proximal motifs together to compact the local protein structure. We further designed and placed glyco-linkers in the unusual form of glyco-bridge and glyco-hairpin at the interfaces between domains and monomers with higher structural level, respectively, which conferred dramatically higher kinetic stability and thermodynamic stability than the inherent N-glycans. Our study not only provides unique insight into the interactions between glycans and proteins from a quaternary structure perspective but also facilitates the rational design of N-glycans as general tools that can enhance protein stability. |
Databáze: | OpenAIRE |
Externí odkaz: |