Chaperone-Like Functions of High-Mannose Type and Complex-Type N-Glycans and Their Molecular Basis

• Published in: Journal of biochemistry (Tokyo) Vol. 132; no. 5; pp. 803 - 811
• Main Authors: Jitsuhara, Yuki, Toyoda, Teruko, Itai, Tomokazu, Yamaguchi, Haruki
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.11.2002
• Subjects: Galactose - physiology; glycoprotein; Mannose - physiology; Models, Molecular; Molecular Chaperones - physiology; N-glycan function; N-linked oligosaccharide; Polysaccharides - chemistry; Polysaccharides - physiology; Protein Conformation; Protein Folding; protein stabilization; Ricinus - physiology
• ISSN: 0021-924X; 1756-2651
• DOI: 10.1093/oxfordjournals.jbchem.a003290

It has recently become apparent that high-mannose type N-glycans directly promote protein folding, whereas complex-type ones play a crucial role in the stabilization of protein functional conformations through hydrophobic interactions with the hydrophobic protein surfaces. Here an attempt was made to understand more deeply the molecular basis of these chaperone-like functions with the aid of information obtained from spacefill models of N-glycans. The promotion of protein folding by high-mannose N-glycans seemed to be based on their unique structure, which includes a hydrophobic region similar to the cyclodextrin cavity. The promotive features of high-mannose N-glycans newly observed under various conditions furnished strong support for the view that both intra- and extramolecular high-mannose N-glycans are directly involved in the promotion of protein folding in the endoplasmic reticulum. Further, it was revealed that the N-acetyllactosamine units in complex-type N-glycans have an amphiphilic structure and greatly contribute to the formation of extensive hydrophobic surfaces and, consequently, to the N-glycan-protein hydrophobic interactions. The processing of high-mannose type N-glycans to complex-type ones seems to be an ingenious device to enable the N-glycans to perform these two chaperone-like functions.