Structural insights into modulation of neurexin-neuroligin trans-synaptic adhesion by MDGA1/Neuroligin-2 complex = MDGA1/Neuroligin-2 복합체에 의한 Neurexin-Neuroligin 시냅스 접착 조절에 대한 구조적 해석

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Membrane-associated mucin domain-containing glycosylphosphatidylinositol anchor proteins (MDGAs) bind directly to neuroligin-1 (NL1) and neuroligin-2 (NL2), thereby respectively regulating excitatory and inhibitory synapse development. However, the mechanisms by which MDGAs modulate NL activity to specify development of the two synapse types remain unclear. Here, the crystal structures of human NL2/MDGA1 Ig1-3 complex was determined, revealing their stable 2:2 arrangement with three interaction interfaces. Cell-based assays using structure-guided, site-directed MDGA1 mutants showed that all three contact patches were required for the MDGA’s negative regulation of NL2-mediated synaptogenic activity. Furthermore, MDGA1 competed with neurexins for NL2 via its Ig1 domain. The binding affinities of both MDGA1 and MDGA2 for NL1 and NL2 were similar, consistent with the structural prediction of similar binding interfaces. However, MDGA1 selectively associated with NL2, but not NL1, in vivo. These findings collectively provide structural insights into the mechanism by which MDGAs negatively modulate synapse development governed by NLs/neurexins.
Advisors
Lee, Jie-Ohresearcher이지오researcherKim, Ho Minresearcher김호민researcher
Description
한국과학기술원 :나노과학기술대학원,
Publisher
한국과학기술원
Issue Date
2018
Identifier
325007
Language
eng
Description

학위논문(박사) - 한국과학기술원 : 나노과학기술대학원, 2018.2,[iv, 56 p. :]

Keywords

MDGA1▼aNeuroligin-2▼aNeurexin▼ainhibitory synapse▼asynaptic regulation; MDGA1▼aNeuroligin-2▼aNeurexin▼a억제성 시냅스▼a시냅스 조절

URI
http://hdl.handle.net/10203/264607
Link
http://library.kaist.ac.kr/search/detail/view.do?bibCtrlNo=734276&flag=dissertation
Appears in Collection
NT-Theses_Ph.D.(박사논문)
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