RRC ID 59523
著者 Krahn N, Meier M, Reuten R, Koch M, Stetefeld J, Patel TR.
タイトル Solution Structure of C. elegans UNC-6: A Nematode Paralogue of the Axon Guidance Protein Netrin-1.
ジャーナル Biophys J
Abstract 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 ΔC 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.
巻・号 116(11)
ページ 2121-2130
公開日 2019-6-4
DOI 10.1016/j.bpj.2019.04.033
PII S0006-3495(19)30377-7
PMID 31103237
PMC PMC6554493
MeSH Amino Acid Sequence Axon Guidance* Caenorhabditis elegans Proteins / chemistry* Caenorhabditis elegans Proteins / metabolism Evolution, Molecular Netrin-1 / chemistry* Netrin-1 / metabolism Netrins / chemistry* Netrins / metabolism Osmolar Concentration Protein Domains Sequence Homology, Amino Acid* Solutions
IF 3.665
引用数 1
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