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
|
リソース情報 |
線虫 |
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