High-Resolution Conformation and Backbone Dynamics of a Soluble Aggregate of Apomyoglobin119
The structure and dynamics of soluble misfolded aggregates are poorly understood, despite their importance in protein science and disease. Water-soluble self-associated species that do not become insoluble over time are invaluable tools for high-resolution conformational studies aimed at dissecting...
Published in: | Biophysical Journal |
---|---|
Main Authors: | , , |
Format: | Text |
Language: | English |
Published: |
The Biophysical Society
2011
|
Subjects: | |
Online Access: | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3030155 http://www.ncbi.nlm.nih.gov/pubmed/21281590 https://doi.org/10.1016/j.bpj.2010.12.3722 |
id |
ftpubmed:oai:pubmedcentral.nih.gov:3030155 |
---|---|
record_format |
openpolar |
spelling |
ftpubmed:oai:pubmedcentral.nih.gov:3030155 2023-05-15T18:26:48+02:00 High-Resolution Conformation and Backbone Dynamics of a Soluble Aggregate of Apomyoglobin119 Rajagopalan, Senapathy Kurt, Neşe Cavagnero, Silvia 2011-02-02 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3030155 http://www.ncbi.nlm.nih.gov/pubmed/21281590 https://doi.org/10.1016/j.bpj.2010.12.3722 en eng The Biophysical Society http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3030155 http://www.ncbi.nlm.nih.gov/pubmed/21281590 http://dx.doi.org/10.1016/j.bpj.2010.12.3722 © 2011 by the Biophysical Society. Protein Text 2011 ftpubmed https://doi.org/10.1016/j.bpj.2010.12.3722 2013-09-03T10:32:00Z The structure and dynamics of soluble misfolded aggregates are poorly understood, despite their importance in protein science and disease. Water-soluble self-associated species that do not become insoluble over time are invaluable tools for high-resolution conformational studies aimed at dissecting the determinants of self-association. Here, we characterize the soluble model aggregate apomyoglobin119 (apoMb119), generated upon truncating the residues corresponding to the C-terminal helix of sperm whale apomyoglobin. The secondary structure and backbone dynamics of apoMb119, determined by multidimensional NMR at pH 6.0, reveal the presence of an N-terminal slow-tumbling core and a highly disordered flexible C-terminus displaying residual helicity and large-amplitude backbone motions on the picosecond-to-nanosecond timescale. The backbone of the apoMb119 aggregate assumes progressively increased mobility as residues get further removed from the nonpolar core and closer to the more hydrophilic C-terminal end. This structural motif establishes a useful paradigm for the topology of soluble misfolded protein aggregates in aqueous solution in the absence of stabilizing additives. The partially helical and flexible C-terminus of apoMb119's aggregate is in interesting contrast with the amyloid-related globulomers, which display dangling ends rich in β-strand. Finally, we investigate how a molecular chaperone, the substrate-binding domain of DnaK, interferes with apoMb119's aggregation. Text Sperm whale PubMed Central (PMC) Biophysical Journal 100 3 747 755 |
institution |
Open Polar |
collection |
PubMed Central (PMC) |
op_collection_id |
ftpubmed |
language |
English |
topic |
Protein |
spellingShingle |
Protein Rajagopalan, Senapathy Kurt, Neşe Cavagnero, Silvia High-Resolution Conformation and Backbone Dynamics of a Soluble Aggregate of Apomyoglobin119 |
topic_facet |
Protein |
description |
The structure and dynamics of soluble misfolded aggregates are poorly understood, despite their importance in protein science and disease. Water-soluble self-associated species that do not become insoluble over time are invaluable tools for high-resolution conformational studies aimed at dissecting the determinants of self-association. Here, we characterize the soluble model aggregate apomyoglobin119 (apoMb119), generated upon truncating the residues corresponding to the C-terminal helix of sperm whale apomyoglobin. The secondary structure and backbone dynamics of apoMb119, determined by multidimensional NMR at pH 6.0, reveal the presence of an N-terminal slow-tumbling core and a highly disordered flexible C-terminus displaying residual helicity and large-amplitude backbone motions on the picosecond-to-nanosecond timescale. The backbone of the apoMb119 aggregate assumes progressively increased mobility as residues get further removed from the nonpolar core and closer to the more hydrophilic C-terminal end. This structural motif establishes a useful paradigm for the topology of soluble misfolded protein aggregates in aqueous solution in the absence of stabilizing additives. The partially helical and flexible C-terminus of apoMb119's aggregate is in interesting contrast with the amyloid-related globulomers, which display dangling ends rich in β-strand. Finally, we investigate how a molecular chaperone, the substrate-binding domain of DnaK, interferes with apoMb119's aggregation. |
format |
Text |
author |
Rajagopalan, Senapathy Kurt, Neşe Cavagnero, Silvia |
author_facet |
Rajagopalan, Senapathy Kurt, Neşe Cavagnero, Silvia |
author_sort |
Rajagopalan, Senapathy |
title |
High-Resolution Conformation and Backbone Dynamics of a Soluble Aggregate of Apomyoglobin119 |
title_short |
High-Resolution Conformation and Backbone Dynamics of a Soluble Aggregate of Apomyoglobin119 |
title_full |
High-Resolution Conformation and Backbone Dynamics of a Soluble Aggregate of Apomyoglobin119 |
title_fullStr |
High-Resolution Conformation and Backbone Dynamics of a Soluble Aggregate of Apomyoglobin119 |
title_full_unstemmed |
High-Resolution Conformation and Backbone Dynamics of a Soluble Aggregate of Apomyoglobin119 |
title_sort |
high-resolution conformation and backbone dynamics of a soluble aggregate of apomyoglobin119 |
publisher |
The Biophysical Society |
publishDate |
2011 |
url |
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3030155 http://www.ncbi.nlm.nih.gov/pubmed/21281590 https://doi.org/10.1016/j.bpj.2010.12.3722 |
genre |
Sperm whale |
genre_facet |
Sperm whale |
op_relation |
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3030155 http://www.ncbi.nlm.nih.gov/pubmed/21281590 http://dx.doi.org/10.1016/j.bpj.2010.12.3722 |
op_rights |
© 2011 by the Biophysical Society. |
op_doi |
https://doi.org/10.1016/j.bpj.2010.12.3722 |
container_title |
Biophysical Journal |
container_volume |
100 |
container_issue |
3 |
container_start_page |
747 |
op_container_end_page |
755 |
_version_ |
1766208766903058432 |