Lillebostad, P.A.G.; Raasakka, A.; Hjellbrekke, S.J.; Patil, S.; Røstbø, T.; Hollås, H.; Sakya, S.A.; Szigetvari, P.D.; Vedeler, A.; Kursula, P. Structure of the ALS Mutation Target Annexin A11 Reveals a Stabilising N-Terminal Segment. Biomolecules 2020, 10, 660. https://doi.org/10.3390/biom10040660
Structure of the ALS mutation target annexin A11 reveals a stabilising N-terminal segment
|Author:||Lillebostad, Peder A. G.1; Raasakka, Arne1; Hjellbrekke, Silje J.1;|
1Department of Biomedicine, University of Bergen, Jonas Lies vei 91, 5009 Bergen, Norway
2Faculty of Biochemistry and Molecular Medicine & Biocenter Oulu, University of Oulu, Aapistie 7, 90220 Oulu, Finland
|Online Access:||PDF Full Text (PDF, 4.3 MB)|
|Persistent link:|| http://urn.fi/urn:nbn:fi-fe2020070646964
Multidisciplinary Digital Publishing Institute,
|Publish Date:|| 2020-07-06
The functions of the annexin family of proteins involve binding to Ca2+, lipid membranes, other proteins, and RNA, and the annexins share a common folded core structure at the C terminus. Annexin A11 (AnxA11) has a long N-terminal region, which is predicted to be disordered, binds RNA, and forms membraneless organelles involved in neuronal transport. Mutations in AnxA11 have been linked to amyotrophic lateral sclerosis (ALS). We studied the structure and stability of AnxA11 and identified a short stabilising segment in the N-terminal end of the folded core, which links domains I and IV. The crystal structure of the AnxA11 core highlights main-chain hydrogen bonding interactions formed through this bridging segment, which are likely conserved in most annexins. The structure was also used to study the currently known ALS mutations in AnxA11. Three of these mutations correspond to buried Arg residues highly conserved in the annexin family, indicating central roles in annexin folding. The structural data provide starting points for detailed structure–function studies of both full-length AnxA11 and the disease variants being identified in ALS.
|Type of Publication:||
A1 Journal article – refereed
|Field of Science:||
1182 Biochemistry, cell and molecular biology
This research was funded by the University of Bergen. Synchrotron visits were supported by the EU Framework Programme for Research and Innovation HORIZON 2020 iNEXT and CALIPSOplus programmes, grant numbers 653706 and 730872.
|EU Grant Number:||
(653706) iNEXT - Infrastructure for NMR, EM and X-rays for translational research
© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).