Proposing a minimal set of metrics and methods to predict probabilities of amyloidosis disease and onset age in individuals

Modification of the structural stability of human serum albumin in rheumatoid arthritis

“…To better understand RA pathology and changes in HSA stability, future RA studies should look for potential binding partners by extracting lipids and small molecules from purified serum HSA. Other directions to explore the mechanisms that increase HSA stability are: (1) Using more specific surface modifications or chemical crosslinking reagents to carry out indepth surface probing of HSA, collect specific information about HSA binding partners and coordination changes [93,94], and (2) comparing HSA and CRP protein binding partners in RA and non-RA patients using immunoaffinity purification together with mass spectrometry to understand how a change in CRP concentration could be contributing to HSA interactor changes. Future research into HSA and other related proteins will continue to enhance our understanding of RA-specific pathology and give insights into the development of, and potential treatments for, RA.…”

Quantifying In Situ Structural Stabilities of Human Blood Plasma Proteins Using a Novel Iodination Protein Stability Assay

“…7−9 A change in the protein folding stability (PFS) between conditions may indicate an individual protein's tendency for proper function (stable 2 ), misfolding (less stable 2 ), and aggregation (ultrastable 2 ) and thus quantify the quality of the measured protein. 10 Ideally, such measurement should be made for each protein in the context of the entire proteome to retain the effect from the interactions with other proteins and ligands. However, the experimental techniques available currently limit studies of the PFS at the proteome level.…”

“…The quality of individual proteins can be evaluated in part using protein folding stability (Δ G folding) as a quantifiable metric of protein structure, which is directly related to the 3-dimensional structure and functionality. − Changes in protein folding are frequently associated with changes in stability. For example, the formation of thermodynamically stabile amyloid or aggregate, as is the case for many neurodegenerative diseases. − A change in the protein folding stability (PFS) between conditions may indicate an individual protein’s tendency for proper function (stable), misfolding (less stable), and aggregation (ultrastable) and thus quantify the quality of the measured protein . Ideally, such measurement should be made for each protein in the context of the entire proteome to retain the effect from the interactions with other proteins and ligands.…”

“…Moreover, it is difficult to apply thermal denaturation methods on blood serum, the most common biological source for diagnosis. This is because serum albumin (HSA), the most abundant serum protein, has a relatively high melting temperature , and thus reduces the efficiency of the temperature gradient to aggregate the proteins using thermal cyclers currently commercially available. , Removing HSA prior to thermal denaturation is not a viable answer as that may alter many other proteins’ PFS because HSA also stabilizes many serum proteins. The second general type of MS-based methods use chemical modification which can measure the PFS of different residues across the protein sequence.…”

“…IPSA introduces irreversible iodination of tyrosine (Y) and histidine (H) as well as oxidation of methionine (M) and cystine (C) (Figure B). The additional reporters for the PFS given by IPSA increase both the breadth of the proteome and the granularity of information within individual proteins . The biggest advantage of IPSA is that it quantifies residue stability, which gives higher resolution to track the PFS change within different regions of a protein.…”