ArticleJournal of molecular biology2008
Fibril growth kinetics reveal a region of beta2-microglobulin important for nucleation and elongation of aggregation.
Article in Journal of molecular biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
41 citing papers in PubMed.
- Article
- Under Conditions of Amyloid Formation Bovine Carbonic Anhydrase B Undergoes Fragmentation by Acid Hydrolysis.Biomolecules · 2021Article
- Bacterial Protein Homeostasis Disruption as a Therapeutic Intervention.Frontiers in molecular biosciences · 2021Review
- Looking Beyond the Core: The Role of Flanking Regions in the Aggregation of Amyloidogenic Peptides and Proteins.Frontiers in neuroscience · 2020Review
- The Early Phase of β2-Microglobulin Aggregation: Perspectives From Molecular Simulations.Frontiers in molecular biosciences · 2020Review
- Examination of Adsorption Orientation of Amyloidogenic Peptides Over Nano-Gold Colloidal Particle Surfaces.International journal of molecular sciences · 2019Article
- Article
- The structure of a βNature communications · 2018Article
- sw ApoMb Amyloid Aggregation under Nondenaturing Conditions: The Role of Native Structure Stability.Biophysical journal · 2017Article
- Understanding co-polymerization in amyloid formation by direct observation of mixed oligomers.Chemical science · 2017Article
- Proline Residues as Switches in Conformational Changes Leading to Amyloid Fibril Formation.International journal of molecular sciences · 2017Article
- Rational design of mutations that change the aggregation rate of a protein while maintaining its native structure and stability.Scientific reports · 2016Article
- ESI-IMS-MS: A method for rapid analysis of protein aggregation and its inhibition by small molecules.Methods (San Diego, Calif.) · 2016Article
- Comparison of the aggregation of homologous β2-microglobulin variants reveals protein solubility as a key determinant of amyloid formation.Journal of molecular biology · 2016Article
- Insights into the consequences of co-polymerisation in the early stages of IAPP and Aβ peptide assembly from mass spectrometry.The Analyst · 2015Article
- A covalent homodimer probing early oligomers along amyloid aggregation.Scientific reports · 2015Article
- Supersaturation-limited and Unlimited Phase Transitions Compete to Produce the Pathway Complexity in Amyloid Fibrillation.The Journal of biological chemistry · 2015Article
- Small liposomes accelerate the fibrillation of amyloid β (1-40).The Journal of biological chemistry · 2015Article
- Wild type beta-2 microglobulin and DE loop mutants display a common fibrillar architecture.PloS one · 2015Article
- Screening and classifying small-molecule inhibitors of amyloid formation using ion mobility spectrometry-mass spectrometry.Nature chemistry · 2015Article
Corrections and comments
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Authors and funding
4 authors.
Funding
Abstract
Amyloid is a highly ordered form of aggregate comprising long, straight and unbranched proteinaceous fibrils that are formed with characteristic nucleation-dependent kinetics in vitro. Currently, the structural molecular mechanism of fibril nucleation and elongation is poorly understood. Here, we investigate the role of the sequence and structure of the initial monomeric precursor in determining the rates of nucleation and elongation of human beta(2)-microglobulin (beta(2)m). We describe the kinetics of seeded and spontaneous (unseeded) fibril growth of wild-type beta(2)m and 12 variants at pH 2.5, targeting specifically an aromatic-rich region of the polypeptide chain (residues 62-70) that has been predicted to be highly amyloidogenic. The results reveal the importance of aromatic residues in this part of the beta(2)m sequence in fibril formation under the conditions explored and show that this region of the polypeptide chain is involved in both the nucleation and the elongation phases of fibril formation. Structural analysis of the conformational properties of the unfolded monomer for each variant using NMR relaxation methods revealed that all variants contain significant non-random structure involving two hydrophobic clusters comprising regions 29-51 and 58-79, the extent of which is critically dependent on the sequence. No direct correlation was observed, however, between the extent of non-random structure in the unfolded state and the rates of fibril nucleation and elongation, suggesting that the early stages of aggregation involve significant conformational changes from the initial unfolded state. Together, the data suggest a model for beta(2)m amyloid formation in which structurally specific interactions involving the highly hydrophobic and aromatic-rich region comprising residues 62-70 provide a complementary interface that is key to the generation of amyloid fibrils for this protein at acidic pH.
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