Sina Djafari Rouhani+, Atanu Acharya++, and Deepika Das+++ +Emory College of Arts and Sciences, ++Georgia Institute of Technology, +++Oxford College of Emory University Human psoriasin (S100A7) protein is a natural antimicrobial peptide that belongs to the S-100 family of proteins that bind Ca2+. Psoriasin provides immunity against the skin disease psoriasis, acts as a putative urinary cancer marker, and shows anti-microbial (anti-bacterial and anti-fungal) activity. Psoriasin is a 22-kDa homodimer with two transition-metal-binding His3Asp sites at the dimer interface. Each monomer contains two cysteine residues which can form disulfide bonds depending on the environment. One mechanism of anti-microbial function of psoriasin depends on the redox state of the protein. Herein, we studied the possible effect of the oxidation states of cysteines on the psoriasin dimer interface which will affect its function. We provide insights into the structural changes of psoriasin by comparative analysis in different conditions for apo and various Zn2+ metallated forms using all-atom molecular dynamics (MD) simulation. We used CHARM36m force field with TIP3 water model in our MD simulations using NAMD. Our analysis showed that in the absence of the disulfide bond between the cysteines, the psoriasin dimer becomes more flexible. Remarkably, removal of the disulfide bond from each monomer reduced hydrogen bonds between monomers, although the cysteines are not directly involved in the dimer interface. Our analysis further emphasizes the role of the disulfide bonds in metal sequestration by the His3Asp sites and provides insight towards a molecular understanding of psoriasin’s anti-microbial activity.

Impact of the disulfide linkage on human psoriasin (S100A7) dimer interface

ACS Fall 2021

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