Robo1 Forms a Compact Dimer-of-Dimers Assembly

被引：27

作者：

Aleksandrova, Nataliia ^{[1
]}

Gutsche, Irina ^{[2
]}

Kandiah, Eaazhisai ^{[2
]}

Avilov, Sergiy V. ^{[1
]}

Petoukhov, Maxim V. ^{[3
,4
,5
,6
]}

Seiradake, Elena ^{[7
]}

McCarthy, Andrew A. ^{[1
]}

机构：

[1] European Mol Biol Lab, Grenoble Outstn, 71 Ave Martyrs, F-38042 Grenoble, France

[2] Univ Grenoble Alpes, CNRS, CEA, IBS, 71 Ave Martyrs, F-38044 Grenoble, France

[3] European Mol Biol Lab, Hamburg Unit, Notkestr 85, D-22607 Hamburg, Germany

[4] Russian Acad Sci, Fed Sci Res Ctr Crystallog & Photon, Leninsky Prospect 59, Moscow 119333, Russia

[5] RAS, AN Frumkin Inst Phys Chem & Electrochem, Leninsky Prospect 31, Moscow 119071, Russia

[6] Russian Acad Sci, NN Semenov Inst Chem Phys, Kosygina St 4, Moscow 119991, Russia

[7] Univ Oxford, Dept Biochem, South Parks Rd, Oxford OX1 3QU, England

来源：

STRUCTURE | 2018年 / 26卷 / 02期

关键词：

AXON GUIDANCE; ROUNDABOUT RECEPTOR; ELECTRON-MICROSCOPY; PROXIMITY LIGATION; PROTEIN-PRODUCTION; HEPARAN-SULFATE; HIGH-RESOLUTION; CELL-SURFACE; HIGH-LEVEL; IN-SITU;

D O I：

10.1016/j.str.2017.12.003

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：

Roundabout (Robo) receptors provide an essential repulsive cue in neuronal development following Slit ligand binding. This important signaling pathway can also be hijacked in numerous cancers, making Slit-Robo an attractive therapeutic target. However, little is known about how Slit binding mediates Robo activation. Here we present the crystal structure of Robo1 Ig1-4 and Robo1 Ig5, together with a negative stain electron microscopy reconstruction of the Robo1 ectodomain. These results show how the Robo1 ectodomain is arranged as compact dimers, mainly mediated by the central Ig domains, which can further interact in a "back-to-back'' fashion to generate a tetrameric assembly. We also observed no change in Robo1 oligomerization upon interaction with the dimeric Slit2-N ligandusing fluorescent imaging. Taken together with previous studies we propose that Slit2-N binding results in a conformational change of Robo1 to trigger cell signaling.

引用

页码：320 / +

页数：13

共 67 条

[1]

[Anonymous], 1982, Small angle x-ray scattering, DOI DOI 10.1002/ACTP.1985.010360520

[2] A time- and cost-efficient system for high-level protein production in mammalian cells [J].

Aricescu, A. Radu ;

Lu, Weixian ;

Jones, E. Yvonne .

ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY, 2006, 62 :1243-1250

[3] ConSurf 2016: an improved methodology to estimate and visualize evolutionary conservation in macromolecules [J].

Ashkenazy, Haim ;

Abadi, Shiran ;

Martz, Eric ;

Chay, Ofer ;

Mayrose, Itay ;

Pupko, Tal ;

Ben-Tal, Nir .

NUCLEIC ACIDS RESEARCH, 2016, 44 (W1) :W344-W350

[4] Time-Resolved Visualisation of Nearly-Native Influenza A Virus Progeny Ribonucleoproteins and Their Individual Components in Live Infected Cells [J].

Avilov, Sergiy ;

Magnus, Julie ;

Cusack, Stephen ;

Naffakh, Nadia .

PLOS ONE, 2016, 11 (03)

[5]

Ba-Charvet KTN, 2001, J NEUROSCI, V21, P4281

[6] A Roundabout Way to Cancer [J].

Ballard, Mimmi S. ;

Hinck, Lindsay .

GUIDANCE MOLECULES IN CANCER AND TUMOR ANGIOGENESIS, 2012, 114 :187-235

[7] Crystal structure of the extracellular juxtamembrane region of Robo1 [J].

Barak, Reut ;

Lahmi, Roxane ;

Gevorkyan-Airapetov, Lada ;

Levy, Eliad ;

Tzur, Amit ;

Opatowsky, Yarden .

JOURNAL OF STRUCTURAL BIOLOGY, 2014, 186 (02) :283-291

[8]

Bricogne G., 2016, BUSTER GLOBAL PHASIN

[9] Slit proteins bind robe receptors and have an evolutionarily conserved role in repulsive axon guidance [J].

Brose, K ;

Bland, KS ;

Wang, KH ;

Arnott, D ;

Henzel, W ;

Goodman, CS ;

Tessier-Lavigne, M ;

Kidd, T .

CELL, 1999, 96 (06) :795-806

[10] Evidence for the existence of two Robo3 isoforms with divergent biochemical properties [J].

Camurri, L ;

Mambetisaeva, E ;

Davies, D ;

Parnavelas, J ;

Sundaresan, V ;

Andrews, W .

MOLECULAR AND CELLULAR NEUROSCIENCE, 2005, 30 (04) :485-493

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