Structural basis of negative regulation of thioredoxin by thioredoxin-interacting protein = TRX-TXNIP 복합체 결정 구조를 이용한 TXNIP의 TRX 기능조절 기작 연구

Cited 0 time in webofscience Cited 0 time in scopus
  • Hit : 465
  • Download : 0
TXNIP has a large number of TRX-dependent and -independent functions in many biological systems. In the TRX-dependent manner, TXNIP, as a negative regulator of TRX, modulates the redox system by binding to TRX and inhibiting its function. Thus, elucidation of regulatory mechanism in the TRX-TXNIP system will improve our understanding of how TRX behaves in cells and whole organisms, both under normal conditions and in human disease. Together with coimmunoprecipitation assays and NMR experiment results, crystallo-graphic results provide insight into the molecular basis of the negative regulation of TRX by TXNIP. Disulfide switching event is necessary for binding to TRX and inhibiting its activity. The interaction between TRX and TXNIP molecules causes the disulfide bond switching from interprotomer disulfide bond between Cys63 and Cys247 to interdomain Cys63-Cys190 disulfide bond and intermolecular TXNIP Cys247-TRX Cys32 disulfide bond. This disulfide switching event results in different structural rearrangement from those of arrestin family. The intermolecular disulfide bond in the TRX-TXNIP complex is susceptible to the level of oxidative stress such as ROS. This mode of disulfide switching, revealed here for the first time to our knowledge, provides the key insight into the negative regulation of TRX by TXNIP.
Advisors
Lee, Jie-Ohresearcher이지오researcher
Description
한국과학기술원 :화학과,
Publisher
한국과학기술원
Issue Date
2013
Identifier
325007
Language
eng
Description

학위논문(박사) - 한국과학기술원 : 화학과, 2013.8 ,[iv, 60 p. :]

Keywords

TRX; TXNIP; redox; oxidative stress; 티록신; 산화; 환원; 항성성

URI
http://hdl.handle.net/10203/222487
Link
http://library.kaist.ac.kr/search/detail/view.do?bibCtrlNo=657374&flag=dissertation
Appears in Collection
CH-Theses_Ph.D.(박사논문)
Files in This Item
There are no files associated with this item.

qr_code

  • mendeley

    citeulike


rss_1.0 rss_2.0 atom_1.0