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Updated: Aug 25, 2026

Resin-Assisted Capture Coupled with Isobaric Tandem Mass Tag Labeling for Multiplexed Quantification of Protein Thiol Oxidation
Published on: June 21, 2021
Differences in biochemical properties and in biological function between human SP-A1 and SP-A2 variants, and the
Guirong Wang1, Sandra R Bates-Kenney, Jian-Qin Tao
1Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA.
Abstract:
The human surfactant protein A (SP-A) locus consists of two functional genes, SP-A1 and SP-A2, with several alleles characterized for each gene. Functional variations between SP-A1 and SP-A2 variants either before or after ozone exposure have been observed. To understand the basis of these differences, we studied SP-A1 and SP-A2 variants by comparing coding sequences, oligomerization patterns under various conditions, composition of oligomers with regard to amino terminal sequence isoforms, biological activity (regulation of phosphatidylcholine (PC) secretion by alveolar type II cells), and the impact of ozone-induced oxidation. We found that (i) the SP-A1 (6A(4)) allele is the most divergent from all SP-A2 alleles, particularly from the SP-A2 (1A(1)). (ii) Differences exist in oligomerization among SP-A1, SP-A2, and coexpressed SP-A1/SP-A2, with higher order multimers (i.e., consisting of more subunits) observed for SP-A1 than for SP-A2 variants. Differences among SP-A1 or SP-A2 gene products are minimal. (iii) Amino acid variants in the amino terminal sequences are observed after signal peptide removal, including variants with an extra cysteine. (iv) Oxidation is observed after ozone exposure, involving several SP-A residues that include cysteine, methionine, and tryptophan. (v) The SP-A2 variant (1A(0)) and the coexpressed protein 1A(0)/6A(2) inhibit ATP-stimulated PC secretion from alveolar type II cells to a greater extent than SP-A1 (6A(2)), a biologic activity that was susceptible to ozone treatment.
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