Structure of the ALS Mutation Target Annexin A11 Reveals a Stabilising N-Terminal Segment
The functions of the annexin family of proteins involve binding to Ca<sup>2+</sup>, 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, b...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-04-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/10/4/660 |
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| author | Peder A. G. Lillebostad Arne Raasakka Silje J. Hjellbrekke Sudarshan Patil Trude Røstbø Hanne Hollås Siri A. Sakya Peter D. Szigetvari Anni Vedeler Petri Kursula |
| author_facet | Peder A. G. Lillebostad Arne Raasakka Silje J. Hjellbrekke Sudarshan Patil Trude Røstbø Hanne Hollås Siri A. Sakya Peter D. Szigetvari Anni Vedeler Petri Kursula |
| author_sort | Peder A. G. Lillebostad |
| collection | DOAJ |
| description | The functions of the annexin family of proteins involve binding to Ca<sup>2+</sup>, 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. |
| first_indexed | 2024-03-10T20:15:49Z |
| format | Article |
| id | doaj.art-cf945f75a36f4d35b18c7f8a95f28d2f |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-10T20:15:49Z |
| publishDate | 2020-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-cf945f75a36f4d35b18c7f8a95f28d2f2023-11-19T22:37:18ZengMDPI AGBiomolecules2218-273X2020-04-0110466010.3390/biom10040660Structure of the ALS Mutation Target Annexin A11 Reveals a Stabilising N-Terminal SegmentPeder A. G. Lillebostad0Arne Raasakka1Silje J. Hjellbrekke2Sudarshan Patil3Trude Røstbø4Hanne Hollås5Siri A. Sakya6Peter D. Szigetvari7Anni Vedeler8Petri Kursula9Department of Biomedicine, University of Bergen, Jonas Lies vei 91, 5009 Bergen, NorwayDepartment of Biomedicine, University of Bergen, Jonas Lies vei 91, 5009 Bergen, NorwayDepartment of Biomedicine, University of Bergen, Jonas Lies vei 91, 5009 Bergen, NorwayDepartment of Biomedicine, University of Bergen, Jonas Lies vei 91, 5009 Bergen, NorwayDepartment of Biomedicine, University of Bergen, Jonas Lies vei 91, 5009 Bergen, NorwayDepartment of Biomedicine, University of Bergen, Jonas Lies vei 91, 5009 Bergen, NorwayDepartment of Biomedicine, University of Bergen, Jonas Lies vei 91, 5009 Bergen, NorwayDepartment of Biomedicine, University of Bergen, Jonas Lies vei 91, 5009 Bergen, NorwayDepartment of Biomedicine, University of Bergen, Jonas Lies vei 91, 5009 Bergen, NorwayDepartment of Biomedicine, University of Bergen, Jonas Lies vei 91, 5009 Bergen, NorwayThe functions of the annexin family of proteins involve binding to Ca<sup>2+</sup>, 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.https://www.mdpi.com/2218-273X/10/4/660annexin A11crystal structuresolution structurecalcium bindingmembrane bindingprotein stability |
| spellingShingle | Peder A. G. Lillebostad Arne Raasakka Silje J. Hjellbrekke Sudarshan Patil Trude Røstbø Hanne Hollås Siri A. Sakya Peter D. Szigetvari Anni Vedeler Petri Kursula Structure of the ALS Mutation Target Annexin A11 Reveals a Stabilising N-Terminal Segment Biomolecules annexin A11 crystal structure solution structure calcium binding membrane binding protein stability |
| title | Structure of the ALS Mutation Target Annexin A11 Reveals a Stabilising N-Terminal Segment |
| title_full | Structure of the ALS Mutation Target Annexin A11 Reveals a Stabilising N-Terminal Segment |
| title_fullStr | Structure of the ALS Mutation Target Annexin A11 Reveals a Stabilising N-Terminal Segment |
| title_full_unstemmed | Structure of the ALS Mutation Target Annexin A11 Reveals a Stabilising N-Terminal Segment |
| title_short | Structure of the ALS Mutation Target Annexin A11 Reveals a Stabilising N-Terminal Segment |
| title_sort | structure of the als mutation target annexin a11 reveals a stabilising n terminal segment |
| topic | annexin A11 crystal structure solution structure calcium binding membrane binding protein stability |
| url | https://www.mdpi.com/2218-273X/10/4/660 |
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