Quality control of secretory proteins containing proline residues in the cis form

2015 Fiscal Year Final Research Report

• Project/Area Number: 25440060
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Functional biochemistry
• Research Institution: National Cardiovascular Center Research Institute
• Principal Investigator: KOKAME KOICHI 国立研究開発法人国立循環器病研究センター, 研究所, 部長 (40270730)
• Co-Investigator(Renkei-kenkyūsha): HIGUCHI YUKA 国立研究開発法人国立循環器病研究センター, 研究所, 非常勤研究員 (30443477)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: タンパク質品質管理 / 小胞体 / プロリン異性化酵素 / ADAMTS13

Outline of Final Research Achievements

Catalysis of cis-trans isomerization of proline residues is often necessary for proper protein folding and function. This study was aimed at understanding the functional importance of the proline isomerization in the quality control of secretory proteins. We used MDTCS domains of ADAMTS13 that contain four proline residues in the cis form as a model protein. As the results using cultured cells and mice, it was revealed that the proline isomerization catalyzed by cyclophilin B in the endoplasmic reticulum was important for secretion of the MDTCS domains. At least a subset of cyclophilin B molecules were associated with the protein complexes involved in endoplasmic reticulum-associated degradation.

Free Research Field

血栓止血学、細胞ストレス応答学