2010
DOI: 10.1002/pro.419
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DE‐loop mutations affect β2 microglobulin stability, oligomerization, and the low‐pH unfolded form

Abstract: b2 microglobulin (b2m) 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 b2m aggregation, several b2m mutants have been previously studied. Among these, three single-residue mutations in the loop connecting strands D and E (W60G, W60V, D59P) h… Show more

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Cited by 44 publications
(76 citation statements)
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“…10,11 Thus, analysis of the number of hydrogen bonds in the loop regions for wt β2m and D59P will provide key insights into the enhanced amyloidogenic propensity of D59P. The superimposed structures of the wt β2m and D59P highlight enhanced fluctuations in the loop regions for D59P (Figure 4).…”
Section: Hydrogen Bond Analysis In the Loop Regionsmentioning
confidence: 99%
“…10,11 Thus, analysis of the number of hydrogen bonds in the loop regions for wt β2m and D59P will provide key insights into the enhanced amyloidogenic propensity of D59P. The superimposed structures of the wt β2m and D59P highlight enhanced fluctuations in the loop regions for D59P (Figure 4).…”
Section: Hydrogen Bond Analysis In the Loop Regionsmentioning
confidence: 99%
“…Protein stability was evaluated by Far-UV circular dichroism (CD) as in [3]; protein aggregation propensity was assessed by thioflavin T fluorescence at 450 nm.…”
Section: Background Beta-2 Microglobulin (β2m) Is Part Of the Major mentioning
confidence: 99%
“…The PDB Ids of the structures were presented in Table 1. A total of 169 natural mutations were reported as polymorphic mutations or natural variants for A chains i.e., type I and there were mainly three type II mutations reported for all the β2m chains [9][10][11][12][19][20][21]. The stereochemical details of the wild-type structures of the MHCs so obtained from PDB were analyzed by Verify3D [20][21][22] and Procheck, and Ramachandran plots [23] were drawn.…”
Section: Collection and Validation Of Mutation Datamentioning
confidence: 99%
“…In several renal failure disorders where the patients need to go through long-term dialysis, dialysis-related amyloidosis (DRA) appears. This amyloid formation has severe effects on skeletal joints and their functionality [9][10][11][12]. Amyloid formations have been shown to have multiple structural variants, using the same monomeric subunit, and amyloids are functionally unique [13].…”
mentioning
confidence: 99%