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Coassembly of Peptides Derived from β-Sheet Regions of β-Amyloid
[Image: see text] In this paper, we investigate the coassembly of peptides derived from the central and C-terminal regions of the β-amyloid peptide (Aβ). In the preceding paper, J. Am. Chem. Soc.2016, DOI: 10.1021/jacs.6b06000, we established that peptides containing residues 17–23 (LVFFAED) from th...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical
Society
2016
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5089069/ https://www.ncbi.nlm.nih.gov/pubmed/27642763 http://dx.doi.org/10.1021/jacs.6b06001 |
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author | Truex, Nicholas L. Nowick, James S. |
author_facet | Truex, Nicholas L. Nowick, James S. |
author_sort | Truex, Nicholas L. |
collection | PubMed |
description | [Image: see text] In this paper, we investigate the coassembly of peptides derived from the central and C-terminal regions of the β-amyloid peptide (Aβ). In the preceding paper, J. Am. Chem. Soc.2016, DOI: 10.1021/jacs.6b06000, we established that peptides containing residues 17–23 (LVFFAED) from the central region of Aβ and residues 30–36 (AIIGLMV) from the C-terminal region of Aβ assemble to form homotetramers consisting of two hydrogen-bonded dimers. Here, we mix these tetramer-forming peptides and determine how they coassemble. Incorporation of a single (15)N isotopic label into each peptide provides a spectroscopic probe with which to elucidate the coassembly of the peptides by (1)H,(15)N HSQC. Job’s method of continuous variation and nonlinear least-squares fitting reveal that the peptides form a mixture of heterotetramers in 3:1, 2:2, and 1:3 stoichiometries, in addition to the homotetramers. These studies also establish the relative stability of each tetramer and show that the 2:2 heterotetramer predominates. (15)N-Edited NOESY shows the 2:2 heterotetramer comprises two different homodimers, rather than two heterodimers. The peptides within the heterotetramer segregate in forming the homodimer subunits, but the two homodimers coassemble in forming the heterotetramer. These studies show that the central and C-terminal regions of Aβ can preferentially segregate within β-sheets and that the resulting segregated β-sheets can further coassemble. |
format | Online Article Text |
id | pubmed-5089069 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | American Chemical
Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-50890692017-09-19 Coassembly of Peptides Derived from β-Sheet Regions of β-Amyloid Truex, Nicholas L. Nowick, James S. J Am Chem Soc [Image: see text] In this paper, we investigate the coassembly of peptides derived from the central and C-terminal regions of the β-amyloid peptide (Aβ). In the preceding paper, J. Am. Chem. Soc.2016, DOI: 10.1021/jacs.6b06000, we established that peptides containing residues 17–23 (LVFFAED) from the central region of Aβ and residues 30–36 (AIIGLMV) from the C-terminal region of Aβ assemble to form homotetramers consisting of two hydrogen-bonded dimers. Here, we mix these tetramer-forming peptides and determine how they coassemble. Incorporation of a single (15)N isotopic label into each peptide provides a spectroscopic probe with which to elucidate the coassembly of the peptides by (1)H,(15)N HSQC. Job’s method of continuous variation and nonlinear least-squares fitting reveal that the peptides form a mixture of heterotetramers in 3:1, 2:2, and 1:3 stoichiometries, in addition to the homotetramers. These studies also establish the relative stability of each tetramer and show that the 2:2 heterotetramer predominates. (15)N-Edited NOESY shows the 2:2 heterotetramer comprises two different homodimers, rather than two heterodimers. The peptides within the heterotetramer segregate in forming the homodimer subunits, but the two homodimers coassemble in forming the heterotetramer. These studies show that the central and C-terminal regions of Aβ can preferentially segregate within β-sheets and that the resulting segregated β-sheets can further coassemble. American Chemical Society 2016-09-19 2016-10-26 /pmc/articles/PMC5089069/ /pubmed/27642763 http://dx.doi.org/10.1021/jacs.6b06001 Text en Copyright © 2016 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 | Truex, Nicholas L. Nowick, James S. Coassembly of Peptides Derived from β-Sheet Regions of β-Amyloid |
title | Coassembly
of Peptides Derived from β-Sheet
Regions of β-Amyloid |
title_full | Coassembly
of Peptides Derived from β-Sheet
Regions of β-Amyloid |
title_fullStr | Coassembly
of Peptides Derived from β-Sheet
Regions of β-Amyloid |
title_full_unstemmed | Coassembly
of Peptides Derived from β-Sheet
Regions of β-Amyloid |
title_short | Coassembly
of Peptides Derived from β-Sheet
Regions of β-Amyloid |
title_sort | coassembly
of peptides derived from β-sheet
regions of β-amyloid |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5089069/ https://www.ncbi.nlm.nih.gov/pubmed/27642763 http://dx.doi.org/10.1021/jacs.6b06001 |
work_keys_str_mv | AT truexnicholasl coassemblyofpeptidesderivedfrombsheetregionsofbamyloid AT nowickjamess coassemblyofpeptidesderivedfrombsheetregionsofbamyloid |