ArticleProtein science : a publication of the Protein Society2010
DE-loop mutations affect beta2 microglobulin stability, oligomerization, and the low-pH unfolded form.
Article in Protein science : a publication of the Protein Society, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 46 citations in OpenAlex.
- Conformational Stability and Dynamics in Crystals Recapitulate Protein Behavior in Solution.Biophysical journal · 2020Article
- Collagen I Weakly Interacts with the β-Sheets of βJournal of the American Chemical Society · 2020Article
- The Early Phase of β2-Microglobulin Aggregation: Perspectives From Molecular Simulations.Frontiers in molecular biosciences · 2020Review
- The Early Phase of β2m Aggregation: An Integrative Computational Study Framed on the D76N Mutant and the ΔN6 Variant.Biomolecules · 2019Article
- Platelet-derived β2M regulates monocyte inflammatory responses.JCI insight · 2019Article
- Insights into the effects of N-glycosylation on the characteristics of the VC1 domain of the human receptor for advanced glycation end products (RAGE) secreted by Pichia pastoris.Glycoconjugate journal · 2019Article
- Increased β-Sheet Dynamics and D-E Loop Repositioning Are Necessary for Cu(II)-Induced Amyloid Formation by β-2-Microglobulin.Biochemistry · 2017Article
- Stepwise unfolding of human βEuropean biophysics journal : EBJ · 2017Article
- α-Synuclein is a Novel Microtubule Dynamase.Scientific reports · 2016Article
- Rational design of mutations that change the aggregation rate of a protein while maintaining its native structure and stability.Scientific reports · 2016Article
- A covalent homodimer probing early oligomers along amyloid aggregation.Scientific reports · 2015Article
- Decoding the Structural Bases of D76N ß2-Microglobulin High Amyloidogenicity through Crystallography and Asn-Scan Mutagenesis.PloS one · 2015Article
- Wild type beta-2 microglobulin and DE loop mutants display a common fibrillar architecture.PloS one · 2015Article
- A simulated intermediate state for folding and aggregation provides insights into ΔN6 β2-microglobulin amyloidogenic behavior.PLoS computational biology · 2014Article
- Insights into the role of the beta-2 microglobulin D-strand in amyloid propensity revealed by mass spectrometry.Molecular bioSystems · 2014Article
- Class I major histocompatibility complex, the trojan horse for secretion of amyloidogenic β2-microglobulin.The Journal of biological chemistry · 2014Article
- Assessing the effect of loop mutations in the folding space of β2-microglobulin with molecular dynamics simulations.International journal of molecular sciences · 2013Article
- Structure, stability, and aggregation of β-2 microglobulin mutants: insights from a Fourier transform infrared study in solution and in the crystalline state.Biophysical journal · 2012Article
- Understanding the complex mechanisms of β2-microglobulin amyloid assembly.The FEBS journal · 2011Review
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Beta2 microglobulin (beta2m) is the light chain of class-I major histocompatibility complex (MHC-I). Its accumulation in the blood of patients affected by kidney failure leads to amyloid deposition around skeletal joints and bones, a severe condition known as Dialysis Related Amyloidosis (DRA). In an effort to dissect the structural determinants of beta2m aggregation, several beta2m mutants have been previously studied. Among these, three single-residue mutations in the loop connecting strands D and E (W60G, W60V, D59P) have been shown to affect beta2m amyloidogenic properties, and are here considered. To investigate the biochemical and biophysical properties of wild-type (w.t.) beta2m and the three mutants, we explored thermal unfolding by Trp fluorescence and circular dichroism (CD). The W60G mutant reveals a pronounced increase in conformational stability. Protein oligomerization and reduction kinetics were investigated by electrospray-ionization mass spectrometry (ESI-MS). All the mutations analyzed here reduce the protein propensity to form soluble oligomers, suggesting a role for the DE-loop in intermolecular interactions. A partially folded intermediate, which may be involved in protein aggregation induced by acids, accumulates for all the tested proteins at pH 2.5 under oxidizing conditions. Moreover, the kinetics of disulfide reduction reveals specific differences among the tested mutants. Thus, beta2m DE-loop mutations display long-range effects, affecting stability and structural properties of the native protein and its low-pH intermediate. The evidence presented here hints to a crucial role played by the DE-loop in determining the overall properties of native and partially folded beta2m.
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