Regulation of ErbB receptors by N-glycans

2016 Fiscal Year Final Research Report

• Project/Area Number: 26440058
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Functional biochemistry
• Research Institution: Sapporo Medical University
• Principal Investigator: TAKAHASHI MOTOKO 札幌医科大学, 医学部, 准教授 (00303941)
• Co-Investigator(Renkei-kenkyūsha): ARIKI Shigeru 札幌医科大学, 医学部, 准教授 (80464478) ; WADA Yoshinao 地方独立行政法人大阪府立病院機構, 大阪府立母子保健総合医療センター, 研究所長 (00250340)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: N型糖鎖 / 糖鎖生物学 / 糖タンパク質 / 増殖因子受容体 / EGFR / ErbB受容体

Outline of Final Research Achievements

The fundamental role of the glycan chain is to modify the physicochemical properties of target molecules. The aim of this study is to determine the mechanisms by which N-glycans regulate the function and structure of ErbB. First, we improved the purification efficiency of recombinant soluble ErbB (sErbB) over 100-fold. It was observed that the sEGFR N418Q N-glycan deletion mutant suppressed EGF signaling more effectively than the wild type. The crystal structure of the sErbB3 N418Q N-glycan deletion mutant revealed that the static structure of sErbB3 is not altered by the deletion of the N-glycan. In contrast, the thermostability of sErbB3 N418Q was reduced compared to the wild type. These results indicate that the N-glycan on N418 of ErbB3 is involved in the conformational stability of sErbB3, and the deletion of the N-glycan would increase the flexibility of the molecule.

Free Research Field

生化学、糖鎖生物学