Structural basis for the cell-cell communication at the neuro-immune interface

2016 Fiscal Year Final Research Report

• Project Area: Analysis and synthesis of multi-dimensional immune organ network
• Project/Area Number: 24111006
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Osaka University
• Principal Investigator: TAKAGI JUNICHI 大阪大学, たんぱく質研究所, 教授 (90212000)
• Co-Investigator(Kenkyū-buntansha): 北郷 悠 大阪大学, たんぱく質研究所, 助教 (60507185)
• Co-Investigator(Renkei-kenkyūsha): IWASAKI Kenji 大阪大学, 蛋白質研究所, 准教授 (20342751)
• Project Period (FY): 2012-06-28 – 2017-03-31
• Keywords: 免疫-神経インターフェイス / X線結晶構造解析 / 電子顕微鏡イメージング / インテグリン / セマフォリン

Outline of Final Research Achievements

In this research I aimed at understanding the molecular mechanism of cellular signal reception from the immune organs via direct cell-cell attachments using structural methods. The major methods include x-ray crystallography and electron microscopy (EM). As a result, we determined for the first time the three dimensional structure of the laminin receptor α6β1 integrin at atomic resolution. We also deduced the signaling mechanism of plexins, the semaphorin receptors, by using EM imaging technique. Other accomplishments include the isolation of a macrocyclic peptide that modulates plexinB1 signaling via allosteric mechanism, together with the clarification of its mode of action by crystallography. We also discovered multiple key molecules on neuronal cells or stem cells implicated in the homeostasis, and performed biochemical as well as structural analyses to elucidate inter-cellular signaling mechanisms in a broad biological contexts.

Free Research Field

構造生物学