Solution Structure of C. elegans UNC-6: A Nematode Paralogue of the Axon Guidance Protein Netrin-1

被引:7
作者
Krahn, Natalie [1 ]
Meier, Markus [2 ]
Reuten, Raphael [3 ]
Koch, Manuel [4 ,5 ]
Stetefeld, Joerg [2 ,6 ]
Patel, Trushar R. [7 ,8 ,9 ,10 ]
机构
[1] Yale Univ, Dept Mol Biophys & Biochem, New Haven, CT USA
[2] Univ Manitoba, Dept Chem, Winnipeg, MB, Canada
[3] Univ Copenhagen, Biotech Res & Innovat Ctr, Copenhagen, Denmark
[4] Univ Cologne, Med Fac, Inst Dent Res & Oral Musculoskeletal Biol, Cologne, Germany
[5] Univ Cologne, Med Fac, Ctr Biochem, Cologne, Germany
[6] Univ Manitoba, Biochem & Med Genet, Winnipeg, MB, Canada
[7] Univ Lethbridge, Alberta RNA Res & Training Inst, Dept Chem & Biochem, Lethbridge, AB, Canada
[8] Univ Calgary, Cumming Sch Med, Dept Microbiol Immunol & Infect Dis, Calgary, AB, Canada
[9] Univ Alberta, DiscoveryLab, Edmonton, AB, Canada
[10] Univ Alberta, Li Ka Shing Inst Virol, Edmonton, AB, Canada
基金
加拿大自然科学与工程研究理事会;
关键词
MIGRATIONS; BINDING; SHAPE; CUES; DISTRIBUTIONS; RECOGNITION; REVEALS; DOMAINS; CELLS;
D O I
10.1016/j.bpj.2019.04.033
中图分类号
Q6 [生物物理学];
学科分类号
071011 ;
摘要
UNCoordinated-6 (UNC-6) was the first member of the netrin family to be discovered in Caenorhabditis elegans. With homology to human netrin-1, it is a key signaling molecule involved in directing axon migration in nematodes. Similar to netrin-1, UNC-6 interacts with multiple receptors (UNC-5 and UNC-40, specifically) to guide axon migration in development. As a result of the distinct evolutionary path of UNC-6 compared to vertebrate netrins, we decided to employ an integrated approach to study its solution behavior and compare it to the high-resolution structure we previously published on vertebrate netrins. Dynamic light scattering and analytical ultracentrifugation on UNC-6 (with and without its C-domain) solubilized in a low-ionic strength buffer suggested that UNC-6 forms high-order oligomers. An increase in the buffer ionic strength resulted in a more homogeneous preparation of UNC-6, that was used for subsequent solution x-ray scattering experiments. Our biophysical analysis of UNC-6 Delta C solubilized in a high-ionic strength buffer suggested that it maintains a similar head-to-stalk arrangement as netrins -1 and -4. This phenomenon is thought to play a role in the signaling behavior of UNC-6 and its ability to move throughout the extracellular matrix.
引用
收藏
页码:2121 / 2130
页数:10
相关论文
共 46 条
  • [1] Netrin-1: Diversity in development
    Bradford, DanaKai
    Cole, Stacey J.
    Cooper, Helen M.
    [J]. INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY, 2009, 41 (03) : 487 - 493
  • [2] Calculations and Publication-Quality Illustrations for Analytical Ultracentrifugation Data
    Brautigam, Chad A.
    [J]. ANALYTICAL ULTRACENTRIFUGATION, 2015, 562 : 109 - 133
  • [3] A new adaptive grid-size algorithm for the simulation of sedimentation velocity profiles in analytical ultracentrifugation
    Brown, Patrick H.
    Schuck, Peter
    [J]. COMPUTER PHYSICS COMMUNICATIONS, 2008, 178 (02) : 105 - 120
  • [4] Macromolecular size-and-shape distributions by sedimentation velocity analytical ultracentrifugation
    Brown, Patrick H.
    Schuck, Peter
    [J]. BIOPHYSICAL JOURNAL, 2006, 90 (12) : 4651 - 4661
  • [5] Dam J, 2004, METHOD ENZYMOL, V384, P185
  • [6] Activation of 2′ 5′-Oligoadenylate Synthetase by Stem Loops at the 5′-End of the West Nile Virus Genome
    Deo, Soumya
    Patel, Trushar R.
    Dzananovic, Edis
    Booy, Evan P.
    Zeid, Khalid
    McEleney, Kevin
    Harding, Stephen E.
    McKenna, Sean A.
    [J]. PLOS ONE, 2014, 9 (03):
  • [7] Floor-plate-derived netrin-1 is dispensable for commissural axon guidance
    Dominici, Chloe
    Moreno-Bravo, Juan Antonio
    Puiggros, Sergi Roig
    Rappeneau, Quentin
    Rama, Nicolas
    Vieugue, Pauline
    Bernet, Agnes
    Mehlen, Patrick
    Chedotal, Alain
    [J]. NATURE, 2017, 545 (7654) : 350 - +
  • [8] Recognition of viral RNA stem-loops by the tandem double-stranded RNA binding domains of PKR
    Dzananovic, Edis
    Patel, Trushar R.
    Deo, Soumya
    McEleney, Kevin
    Stetefeld, Joerg
    McKenna, Sean A.
    [J]. RNA, 2013, 19 (03) : 333 - 344
  • [9] The Crystal Structure of Netrin-1 in Complex with DCC Reveals the Bifunctionality of Netrin-1 As a Guidance Cue
    Finci, Lorenzo I.
    Krueger, Nina
    Sun, Xiaqin
    Zhang, Jie
    Chegkazi, Magda
    Wu, Yu
    Schenk, Gundolf
    Mertens, Haydyn D. T.
    Svergun, Dmitri I.
    Zhang, Yan
    Wang, Jia-huai
    Meijers, Rob
    [J]. NEURON, 2014, 83 (04) : 839 - 849
  • [10] Scatter: software for the analysis of nano- and mesoscale small-angle scattering
    Foerster, S.
    Apostol, L.
    Bras, W.
    [J]. JOURNAL OF APPLIED CRYSTALLOGRAPHY, 2010, 43 : 639 - 646