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Structural studies revealed that S100A7 functions as (Ca2+)-bound homodimer, which can load two Zn2+ ions at symmetrically disposed sites across the dimer interface using residues His-86 and His-90 from one subunit and residues His-17 and Asp-24 from the other (Brodersen DE et al. 1999). Binding of Zn2+ is believed to stabilize the dimer and potentially mediate S100A7 function during infection (Brodersen DE et al. 1999).
S100A7 and its paralog, S100A7A (S100A15 or koebnerisin) display 93% sequence identity (Wolf R et al. 2011; Murray JI et al. 2012). Human S100A7A (S100A15) showed antimicrobial activity against E. coli (Büchau AS et al. 2007). Moreover, structural and solution binding studies revealed similar affinities of zinc ion for S100A7 and S100A7A (S100A15) (Murray JI et al. 2012). Though the Reactome project describes psoriacin (S100A7) and koebnerisin (S100A7A) as antimicrobial proteins with the metal-chelating properties, additional studies are needed to more fully define the contribution of S100A7 and S100A7A to nutritional immunity.
Particularly high expression of S100A7 and S100A7A was observed in inflamed psoriatic lesions, which are characterized by disturbed epidermal differentiation and inflammation (Madsen P et al. 1991). Circulating leukocytes (PBMCs) of patients with psoriasis produced increased levels of koebnerisin and psoriasin compared to healthy individuals (Batycka-Baran A et al. 2015). Both S100A proteins further acted as 'alarmins' on PBMC to induce proinflammatory cytokines implicated in the pathogenesis of psoriasis, such as IL-1beta, TNFalpha, IL6 and IL8 (Batycka-Baran A et al. 2015). However, inflammatory activities of S100A7 and S100A7A were found to serve distinct roles in epithelial homeostasis, inflammation, and cancer (Hattinger E et al. 2013; Wolf R et al. 2011; Murray JI et al. 2012). S100A7 signals through the receptor for advanced glycation products (RAGE) in a zinc-dependent manner, while S100A15 signals through a yet unidentified G-protein coupled receptor in a zinc-independent manner (Wolf R et al. 2011; Murray JI et al. 2012). Apart from inflammatory skin diseases an elevated exression of S100A7 was found in several epithelial cancers such as squamous cell carcinoma (SCC) of the skin, bladder, lung as well as in in situ ductal breast carcinoma (Celis JE et al. 1996; Al-Haddad S et al. 1999; Emberley ED et al. 2004; Moubayed N et al. 2007; Liu G et al. 2015; Qi Z et al. 2015).