ArticleProtein science : a publication of the Protein Society2000
Removal of the N-terminal hexapeptide from human beta2-microglobulin facilitates protein aggregation and fibril formation.
Article in Protein science : a publication of the Protein Society, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers.
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95 citing papers in PubMed.
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- The effect of mutation on an aggregation-prone protein: An in vivo, in vitro, and in silico analysis.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- The residues 4 to 6 at the N-terminus in particular modulate fibril propagation of β-microglobulin.Acta biochimica et biophysica Sinica · 2022Article
- Generating Ensembles of Dynamic Misfolding Proteins.Frontiers in neuroscience · 2022Review
- Amyloid Formation by Globular Proteins: The Need to Narrow the Gap BetweenFrontiers in molecular biosciences · 2022Review
- Global Proteotoxicity Caused by Human βInternational journal of molecular sciences · 2021Article
- Investigation of D76N βJournal of the American Society for Mass Spectrometry · 2021Article
- Structure of Nanobody Nb23.Molecules (Basel, Switzerland) · 2021Article
- Trypsin Induced Degradation of Amyloid Fibrils.International journal of molecular sciences · 2021Article
- Predicting stable binding modes from simulated dimers of the D76N mutant ofComputational and structural biotechnology journal · 2021Article
- Article
- Insights into a Protein-Nanoparticle System by Paramagnetic Perturbation NMR Spectroscopy.Molecules (Basel, Switzerland) · 2020Article
- Alpha-B-Crystallin Effect on Mature Amyloid Fibrils: Different Degradation Mechanisms and Changes in Cytotoxicity.International journal of molecular sciences · 2020Article
- The role of the IThe Journal of biological chemistry · 2020Article
- Measuring the Energy Barrier of the Structural Change That Initiates Amyloid Formation.Analytical chemistry · 2020Article
- A short motif in the N-terminal region of α-synuclein is critical for both aggregation and function.Nature structural & molecular biology · 2020Article
- Collagen I Weakly Interacts with the β-Sheets of βJournal of the American Chemical Society · 2020Article
35 more citing papers are in PubMed but not listed here.
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15 authors.
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Abstract
The solution structure and stability of N-terminally truncated beta2-microglobulin (deltaN6beta2-m), the major modification in ex vivo fibrils, have been investigated by a variety of biophysical techniques. The results show that deltaN6beta2-m has a free energy of stabilization that is reduced by 2.5 kcal/mol compared to the intact protein. Hydrogen exchange of a mixture of the truncated and full-length proteins at microM concentrations at pH 6.5 monitored by electrospray mass spectrometry reveals that deltaN6beta2-m is significantly less protected than its wild-type counterpart. Analysis of deltaN6beta2-m by NMR shows that this loss of protection occurs in beta strands I, III, and part of II. At mM concentration gel filtration analysis shows that deltaN6beta2-m forms a series of oligomers, including trimers and tetramers, and NMR analysis indicates that strand V is involved in intermolecular interactions that stabilize this association. The truncated species of beta2-microglobulin was found to have a higher tendency to self-associate than the intact molecule, and unlike wild-type protein, is able to form amyloid fibrils at physiological pH. Limited proteolysis experiments and analysis by mass spectrometry support the conformational modifications identified by NMR and suggest that deltaN6beta2-m could be a key intermediate of a proteolytic pathway of beta2-microglobulin. Overall, the data suggest that removal of the six residues from the N-terminus of beta2-microglobulin has a major effect on the stability of the overall fold. Part of the tertiary structure is preserved substantially by the disulfide bridge between Cys25 and Cys80, but the pairing between beta-strands far removed from this constrain is greatly perturbed.
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