Crystal structure of CD40-CD40L complexCD40-CD40L 복합체의 구조에 대한 연구

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The CD40L and CD40 are member of the tumor necrosis factor (TNF) and TNF receptor family protein, respectively. CD40 is a typeⅠtransmembrane protein, which is expressed on B lymphocytes. CD40L is a type Ⅱ transmembrane protein that is expressed by activated T cells. Their interaction induces T-cell mediated B cell activation process. Defects in CD40 or CD40L cause hyper??IgM syndrome (HIGMS) and their interaction play an important role in humoral immune response. The ratio of interaction between CD40 and CD40L is expected to 3: 3 due to the known crystal structure of TNF-TNFR complex. So one CD40L trimer induces three CD40, and this complex transduces intracellular signaling with adaptor, TRAF (tumor necrosis factor receptor associated factor). So the understanding of CD40-CD40L structure is important. In this thesis, we make a crystal of CD40-CD40L complex and solved the crystal structure of CD40-CD40L complex by x-ray diffraction data with 3.5?? resolution. Contrary to expectation, the structure forms 2:3 ratio of CD40 and CD40L in crystal and solution. A series of mutations of CD40L are generated to test the possibility of receptor mutimerization. The Ser132 mutant of CD40L does not alter the overall structure of the receptor-ligand complex with 2:3 ratio, but affect an activity. Therefore these findings suggest that ligand-induced di- or trimerization is necessary but not sufficient for complete activation of CD40.
Advisors
Lee, Jie-Ohresearcher이지오
Description
한국과학기술원 : 화학과,
Publisher
한국과학기술원
Issue Date
2011
Identifier
567309/325007  / 020065038
Language
eng
Description

학위논문(박사) - 한국과학기술원 : 화학과, 2011., [ v, 82 p. ]

Keywords

CD40L; CD40; CD40; CD40L

URI
http://hdl.handle.net/10203/196444
Link
http://library.kaist.ac.kr/search/detail/view.do?bibCtrlNo=567309&flag=dissertation
Appears in Collection
CH-Theses_Ph.D.(박사논문)
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