Study on the molecular mechanism underlying insertion of membrane proteins kinetically unfavorable for the cotranslational insertion pathway into the endoplasmic reticulum membrane

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K07000
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Functional biochemistry
• Research Institution: Kobe University
• Principal Investigator: YAMAMOTO YASUNORI 神戸大学, 医学研究科, 准教授 (30467659)
• Co-Investigator(Renkei-kenkyūsha): SAKISAKA Toshiaki 神戸大学, 大学院医学研究科, 教授 (30467659)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 小胞体 / 膜挿入装置 / ペルオキシソーム形成因子 / 膜変形タンパク質 / reticulon / ヘアピン型膜タンパク質 / テイルアンカー型タンパク質 / CAML-WRB複合体

Outline of Final Research Achievements

Membrane proteins destined for the secretory pathway are first inserted into the endoplasmic reticulum (ER) membrane, followed by delivery to their destinations. Translocon is the most prominent machinery that cotranslationally inserts membrane proteins into the ER membrane. However, if membrane proteins have the ER targeting information near the C-termini, their protein translation reaction will terminate before membrane insertion, precluding taking the cotranslational pathway guided by translocon. In this study, we examined the molecular mechanism how the membrane proteins kinetically unfavorable for translocon were inserted into the ER membrane. We eventually revealed that two peroxisome biogenesis factors, PEX19 and PEX3, constituted an alternative machinery that posttranslationally inserted membrane-shaping proteins into the ER membrane. Besides, we identified a novel ER membrane protein that regulated the posttranslational membrane insertion of tail-anchored proteins.

Free Research Field

生化学