Structural and posttranslational analysis of human calcium‐binding protein, spermatid‐associated 1

• Published in: Journal of cellular biochemistry 2020-12, Vol.121 (12), p.4945-4958
• Main Authors: Marcet‐Palacios, Marcelo, Reyes‐Serratos, Eduardo, Gonshor, Aron, Buck, Robert, Lacy, Paige, Befus, A. D.
• Format: Article
• Language: English
• Subjects: anti‐inflammatory peptides; Autonomic nervous system; Biomarkers; Biotechnology; CABS1; Calcium; Calcium ions; Calcium-binding protein; disordered domains; Domains; Elastase; Energy metabolism; Immune system; in silico analysis; Inflammation; IonCom; I‐TASSER; Leucine; Localization; Magnesium; Mitochondria; Molecular modelling; Phylogeny; posttranslational processing; Primates; Proteins; RaptorX; resilience; Saliva; Sequence analysis; stress; Structure-function relationships; Thiamine; Zinc
• ISSN: 0730-2312; 1097-4644
• DOI: 10.1002/jcb.29824

Recently, we detected a novel biomarker in human saliva called calcium‐binding protein, spermatid‐associated 1 (CABS1). CABS1 protein had previously been described only in testis, and little was known of its characteristics other than it was considered a structurally disordered protein. Levels of human CABS1 (hCABS1) in saliva correlate with stress, whereas smaller sized forms of hCABS1 in saliva are associated with resilience to stress. Interestingly, hCABS1 also has an anti‐inflammatory peptide sequence near its carboxyl terminus, similar to that of a rat prohormone, submandibular rat 1. We performed phylogenetic and sequence analysis of hCABS1. We found that from 72 CABS1 sequences currently annotated in the National Center for Biotechnology Information protein database, only 14 contain the anti‐inflammatory domain “TxIFELL,” all of which are primates. We performed structural unfoldability analysis using PONDER and FoldIndex and discovered three domains that are highly disordered. Predictions of three‐dimensional structure of hCABS1 using RaptorX, IonCom, and I‐TASSER software agreed with these findings. Predicted neutrophil elastase cleavage density also correlated with hCABS1 regions of high structural disorder. Ligand binding prediction identified Ca2+, Mg2+, Zn2+, leucine, and thiamine pyrophosphate, a pattern observed in enzymes associated with energy metabolism and mitochondrial localization. These new observations on hCABS1 raise intriguing questions about the interconnection between the autonomic nervous system, stress, and the immune system. However, the precise molecular mechanisms involved in the complex biology of hCABS1 remain unclear. We provide a detailed in silico analysis of relevant aspects of the structure and function of hCABS1 and postulate extracellular and intracellular roles. The precise molecular mechanisms involved in the complex biology of human calcium‐binding protein, spermatid‐associated 1 (hCABS1) remain unclear. In this manuscript, we provide a detailed in silico analysis of relevant aspects of the structure and function of hCABS1 and postulate extracellular and intracellular roles.