Crystal structure of the extracellular juxtamembrane region of Robo1

被引：16

作者：

Barak, Reut ^{[1
]}

Lahmi, Roxane ^{[1
,2
]}

Gevorkyan-Airapetov, Lada ^{[1
]}

Levy, Eliad ^{[1
]}

Tzur, Amit ^{[1
,2
]}

Opatowsky, Yarden ^{[1
]}

机构：

[1] Bar Ilan Univ, Mina & Everard Goodman Fac Life Sci, IL-5290002 Ramat Gan, Israel

[2] Bar Ilan Univ, Adv Mat & Nanotechnol Inst, IL-5290002 Ramat Gan, Israel

来源：

JOURNAL OF STRUCTURAL BIOLOGY | 2014年 / 186卷 / 02期

基金：

以色列科学基金会;

关键词：

Structure; Slit; Robo1; Receptor; X-ray crystallography; Shedding; PROGRESSIVE SCOLIOSIS; ROUNDABOUT RECEPTOR; GUIDANCE RECEPTORS; SLIT PROTEIN; AXON; MUTATIONS; REPELLENT; CANCER; SCHIZOPHRENIA; CLEAVAGE;

D O I：

10.1016/j.jsb.2014.02.019

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Robo receptors play pivotal roles in neurodevelopment, and their deregulation is implicated in several neuropathological conditions and cancers. To date, the mechanism of Robo activation and regulation remains obscure. Here we present the crystal structure of the juxtamembrane (JM) domains of human Robo1. The structure exhibits unexpectedly high backbone similarity to the netrin and RGM binding region of neogenin and DCC, which are functionally related receptors of Robo1. Comparison of these structures reveals a conserved surface that overlaps with a cluster of oncogenic and neuropathological mutations found in all Robo isoforms. The structure also reveals the intricate folding of the JM linker, which points to its role in Robo1 activation. Further experiments with cultured cells demonstrate that exposure or relief of the folded JM linker results in enhanced shedding of the Robo1 ectodomain. (C) 2014 Elsevier Inc. All rights reserved.

引用

页码：283 / 291

页数：9

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