Mustonen, V., Muruganandam, G., Loris, R., Kursula, P. and Ruskamo, S. (2021), Crystal and solution structure of NDRG1, a membrane-binding protein linked to myelination and tumour suppression. FEBS J, 288: 3507-3529. https://doi.org/10.1111/febs.15660
Crystal and solution structure of NDRG1, a membrane-binding protein linked to myelination and tumour suppression
|Author:||Mustonen, Venla1; Muruganandam, Gopinath2,3; Loris, Remy2,3;|
1Faculty of Biochemistry and Molecular Medicine & Biocenter Oulu, University of Oulu, Finland
2VIB-VUB Center for Structural Biology, Vlaams Instituut voor Biotechnologie, Brussels, Belgium
3Structural Biology Brussels, Department of Bioengineering Sciences, Vrije Universiteit Brussel, Belgium
4Department of Biomedicine, University of Bergen, Norway
|Online Access:||PDF Full Text (PDF, 6.8 MB)|
|Persistent link:|| http://urn.fi/urn:nbn:fi-fe2021062940363
John Wiley & Sons,
|Publish Date:|| 2021-06-29
N-myc downstream-regulated gene 1 (NDRG1) is a tumour suppressor involved in vesicular trafficking and stress response. NDRG1 participates in peripheral nerve myelination, and mutations in the NDRG1 gene lead to Charcot-Marie-Tooth neuropathy. The 43-kDa NDRG1 is considered as an inactive member of the α/β hydrolase superfamily. In addition to a central α/β hydrolase fold domain, NDRG1 consists of a short N terminus and a C-terminal region with three 10-residue repeats. We determined the crystal structure of the α/β hydrolase domain of human NDRG1 and characterised the structure and dynamics of full-length NDRG1. The structure of the α/β hydrolase domain resembles the canonical α/β hydrolase fold with a central β sheet surrounded by α helices. Small-angle X-ray scattering and CD spectroscopy indicated a variable conformation for the N- and C-terminal regions. NDRG1 binds to various types of lipid vesicles, and the conformation of the C-terminal region is modulated upon lipid interaction. Intriguingly, NDRG1 interacts with metal ions, such as nickel, but is prone to aggregation in their presence. Our results uncover the structural and dynamic features of NDRG1, as well as elucidate its interactions with metals and lipids, and encourage studies to identify a putative hydrolase activity of NDRG1.
|Pages:||3507 - 3529|
|Type of Publication:||
A1 Journal article – refereed
|Field of Science:||
This work was funded by Jane and Aatos Erkko Foundation and the Academy of Finland, grant number 315272. The research leading to this result has been supported by the project iNEXT, grant number 653706 and CALIPSOplus, grant number 730872, from the EU Framework Programme for Research and Innovation HORIZON 2020.
|EU Grant Number:||
(653706) iNEXT - Infrastructure for NMR, EM and X-rays for translational research
|Academy of Finland Grant Number:||
315272 (Academy of Finland Funding decision)
© 2020 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.