人Wnt抑制因子-1的WIF结构域的核磁共振结构

NMR structure of the WIF domain of the human Wnt-inhibitory factor-1.

作者信息

Liepinsh Edvards, Bányai László, Patthy László, Otting Gottfried

机构信息

Institute of Organic Synthesis, LV-1006 Riga, Latvia.

出版信息

J Mol Biol. 2006 Mar 31;357(3):942-50. doi: 10.1016/j.jmb.2006.01.047. Epub 2006 Jan 31.

DOI:10.1016/j.jmb.2006.01.047

PMID:16476441

Abstract

The human Wnt-binding protein Wnt-inhibitory factor-1 (WIF-1) comprises an N-terminal WIF module followed by five EGF-like repeats. Here we report the three-dimensional structure of the WIF domain of WIF-1 determined by NMR spectroscopy. The fold consists of an eight-stranded beta-sandwich reminiscent of the immunoglobulin fold. Residual detergent (Brij-35) used in the refolding protocol was found to bind tightly to the WIF domain. The binding site was identified by intermolecular nuclear Overhauser effects observed between the WIF domain and the alkyl chain of the detergent. The results point to a possible role of WIF domains as a recognition motif of Wnt and Drosophila Hedgehog proteins that are activated by palmitoylation.

摘要

人类Wnt结合蛋白Wnt抑制因子-1（WIF-1）由一个N端WIF模块和五个表皮生长因子（EGF）样重复序列组成。在此，我们报道了通过核磁共振光谱法测定的WIF-1的WIF结构域的三维结构。该结构由一个八链β折叠片层组成，类似于免疫球蛋白折叠。发现在重折叠方案中使用的残留去污剂（Brij-35）与WIF结构域紧密结合。通过在WIF结构域和去污剂的烷基链之间观察到的分子间核Overhauser效应确定了结合位点。这些结果表明WIF结构域可能作为Wnt和经棕榈酰化激活的果蝇Hedgehog蛋白的识别基序发挥作用。