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Stability of the N-Terminal Helix and Its Role in Amyloid Formation of Serum Amyloid A
[Image: see text] Colonic amyloidosis is the result of overexpression of the serum amyloid A (SAA) protein in inflammatory bowel disease or colon cancer. Crucial for amyloid formation are the first ten N-terminal residues, which in the crystal structure are a part of a 27-residue long helix. Here, w...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical Society
2018
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6275945/ https://www.ncbi.nlm.nih.gov/pubmed/30533585 http://dx.doi.org/10.1021/acsomega.8b02377 |
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author | Wang, Wenhua Xi, Wenhui Hansmann, Ulrich H. E. |
author_facet | Wang, Wenhua Xi, Wenhui Hansmann, Ulrich H. E. |
author_sort | Wang, Wenhua |
collection | PubMed |
description | [Image: see text] Colonic amyloidosis is the result of overexpression of the serum amyloid A (SAA) protein in inflammatory bowel disease or colon cancer. Crucial for amyloid formation are the first ten N-terminal residues, which in the crystal structure are a part of a 27-residue long helix. Here, we study this 27-residue N-terminal region of SAA by a multiexchange variant of replica exchange molecular dynamics. An ensemble of configurations is observed, dominated by three motifs: the single helix of the crystal structure, a helix-turn-helix configurations, and such where the residues 14–27 are the part of a helix but the first 13 residues form an extended and disordered segment that is prone to aggregation. The single point mutation E9A shifts the equilibrium to the latter motif, indicating the importance of interactions involving this residue for the stability of the SAA protein. |
format | Online Article Text |
id | pubmed-6275945 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | American Chemical Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-62759452018-12-05 Stability of the N-Terminal Helix and Its Role in Amyloid Formation of Serum Amyloid A Wang, Wenhua Xi, Wenhui Hansmann, Ulrich H. E. ACS Omega [Image: see text] Colonic amyloidosis is the result of overexpression of the serum amyloid A (SAA) protein in inflammatory bowel disease or colon cancer. Crucial for amyloid formation are the first ten N-terminal residues, which in the crystal structure are a part of a 27-residue long helix. Here, we study this 27-residue N-terminal region of SAA by a multiexchange variant of replica exchange molecular dynamics. An ensemble of configurations is observed, dominated by three motifs: the single helix of the crystal structure, a helix-turn-helix configurations, and such where the residues 14–27 are the part of a helix but the first 13 residues form an extended and disordered segment that is prone to aggregation. The single point mutation E9A shifts the equilibrium to the latter motif, indicating the importance of interactions involving this residue for the stability of the SAA protein. American Chemical Society 2018-11-29 /pmc/articles/PMC6275945/ /pubmed/30533585 http://dx.doi.org/10.1021/acsomega.8b02377 Text en Copyright © 2018 American Chemical Society This is an open access article published under an ACS AuthorChoice License (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html) , which permits copying and redistribution of the article or any adaptations for non-commercial purposes. |
spellingShingle | Wang, Wenhua Xi, Wenhui Hansmann, Ulrich H. E. Stability of the N-Terminal Helix and Its Role in Amyloid Formation of Serum Amyloid A |
title | Stability of the N-Terminal Helix and Its Role
in Amyloid Formation of Serum Amyloid A |
title_full | Stability of the N-Terminal Helix and Its Role
in Amyloid Formation of Serum Amyloid A |
title_fullStr | Stability of the N-Terminal Helix and Its Role
in Amyloid Formation of Serum Amyloid A |
title_full_unstemmed | Stability of the N-Terminal Helix and Its Role
in Amyloid Formation of Serum Amyloid A |
title_short | Stability of the N-Terminal Helix and Its Role
in Amyloid Formation of Serum Amyloid A |
title_sort | stability of the n-terminal helix and its role
in amyloid formation of serum amyloid a |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6275945/ https://www.ncbi.nlm.nih.gov/pubmed/30533585 http://dx.doi.org/10.1021/acsomega.8b02377 |
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