Universität zu Köln

Krahn, Natalie, Meier, Markus, Reuten, Raphael ORCID: 0000-0002-9434-4108, Koch, Manuel, Stetefeld, Joerg ORCID: 0000-0003-1478-3248 and Patel, Trushar R. ORCID: 0000-0003-0627-2923 (2019). Solution Structure of C. elegans UNC-6: A Nematode Paralogue of the Axon Guidance Protein Netrin-1. Biophys. J., 116 (11). S. 2121 - 2131. CAMBRIDGE: CELL PRESS. ISSN 1542-0086

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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 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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Krahn, Natalie UNSPECIFIED UNSPECIFIED UNSPECIFIED Meier, Markus UNSPECIFIED UNSPECIFIED UNSPECIFIED Reuten, Raphael UNSPECIFIED orcid.org/0000-0002-9434-4108 UNSPECIFIED Koch, Manuel UNSPECIFIED UNSPECIFIED UNSPECIFIED Stetefeld, Joerg UNSPECIFIED orcid.org/0000-0003-1478-3248 UNSPECIFIED Patel, Trushar R. UNSPECIFIED orcid.org/0000-0003-0627-2923 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-138162
DOI:	10.1016/j.bpj.2019.04.033
Journal or Publication Title:	Biophys. J.
Volume:	116
Number:	11
Page Range:	S. 2121 - 2131
Date:	2019
Publisher:	CELL PRESS
Place of Publication:	CAMBRIDGE
ISSN:	1542-0086
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language MIGRATIONS; BINDING; SHAPE; CUES; DISTRIBUTIONS; RECOGNITION; REVEALS; DOMAINS; CELLS Multiple languages Biophysics Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/13816