Disulfide Structure of the Leucine-Rich Repeat C-Terminal Cap and C-Terminal Stalk Region of Nogo-66 Receptor

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• 作者：Dingyi Wen ; Craig P. Wildes ; Laura Silvian ; Lee Walus ; Sha Mi ; Daniel H. S. Lee ; Werner Meier ; and R. Blake Pepinsky
• 刊名：Biochemistry
• 出版年：2005
• 出版时间：December 20, 2005
• 年：2005
• 卷：44
• 期：50
• 页码：16491 - 16501
• 全文大小：338K
• 年卷期：v.44,no.50(December 20, 2005)
• ISSN：1520-4995

文摘

Nogo-66 receptor (NgR1) is a leucine-rich repeat (LRR) protein that forms part of a signalingcomplex modulating axon regeneration. Previous studies have shown that the entire LRR region of NgR1,including the C-terminal cap of the LRR, LRRCT, is needed for ligand binding, and that the adjacentC-terminal region (CT stalk) of the NgR1 contributes to interaction with its coreceptors. To providestructure-based information for these interactions, we analyzed the disulfide structure of full-length NgR1.Our analysis revealed a novel disulfide structure in the C-terminal region of the NgR1, wherein the twoCys residues, Cys-335 and Cys-336, in the CT stalk are disulfide-linked to Cys-266 and Cys-309 in theLRRCT region: Cys-266 is linked to Cys-335, and Cys-309 to Cys-336. The other two Cys residues,Cys-264 and Cys-287, in the LRRCT region are disulfide-linked to each other. The analysis also showedthat Cys-419 and Cys-429, in the CT stalk region, are linked to each other by a disulfide bond. Althoughpublished crystal structures of a recombinant fragment of NgR1 had revealed a disulfide linkage betweenCys-266 and Cys-309 in the LRRCT region and we verified its presence in the corresponding fragment,this is artificially caused by the truncation of the protein, since this linkage was not detected in intactNgR1 or a slightly larger fragment containing Cys-335 and Cys-336. A structural model of the LRRCTwith extended residues 311-344 from the CT stalk region is proposed, and its function in coreceptorbinding is discussed.