Novel Post-translational Modifications in Human Serum Albumin

Abstract

Aim: Identify novel post-translational modifications in human serum albumin. Background: Serum albumin is the most abundant protein in plasma, has many physiological functions, and is in contact with most of the cells and tissues of the human body. Post-translational modifications (PTMs) may affect functions, stability, and localization of albumin. Objective: Identify novel PTMs in human serum albumin by mass spectrometry. Methods: Human serum albumin (HSA) was used for tryptic digestion in-solution or in-gel. Mass spectrometry was applied to identify PTMs in HSA. 3-dimensional modeling was applied to explore potential impact of PTMs on known functions of albumin. Results: Here we report the identification of 61 novel PTMs of human serum albumin. Phosphorylation, glycosylation, nitrosylation, deamidation, methylation, acetylation, palmitoylation, geranylation, and farnesylation are examples of the identified PTMs. Mass spectrometry was used for the identification of PTMs in a purified HSA and HSA from the human plasma. Three-dimensional modeling of albumin with selected PTMs showed the location of these PTMs in the regions involved in interactions of the albumin with drugs, metals, and fatty acids. The location of PTMs in these regions may modify the binding capacity of albumin. Conclusion: This report adds 61 novel PTMs to the catalog of human albumin.

Comparative Analysis of Post-Translational Modifications of Human Serum Albumin Derived from Human Plasma and Recombinant Sources in China

“…Moreover, phosphorylation, glycosylation, acetylation, carbonylation, and methylation modifications of HSA have been documented. As of January 2022, over 210 types of PTMs of HSA have been identified [22]. Given the prolonged circulating half-life of HSA in the body and its exposure to various stressors, preparations of pHSA derived from a blend of healthy human plasma often exhibit diverse PTMs [23].…”

Detection of unusual high molecular form of albumin in blood serum of COVID-19 patients

“…Three-dimensional modeling of albumin with selected PTMs was conducted. Specific PTMs were located in the regions involved in the interactions of the albumin with various medicines, metal cations, and fatty acids [9] The SDS-PAAG electrophoresis demonstrated that the albumin produced by canavanine-treated Hep-G2 cells had a larger (by 4 kDa) molecular weight compared with serum albumin. These cells secreted 79% of proalbumin, 21% of processed albumin, and no preproalbumin, while the untreated Hep-G2 cells secreted 93% of fully processed serum albumin and only 7% of proalbumin [10].…”