S100A7 or S100A7A binds Zn2+

Stable Identifier
R-HSA-6798489
Type
Reaction [binding]
Species
Homo sapiens
Compartment
Synonyms
S100A7/S100A15 binds Zn2+
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Human S100A7 (known as psoriasin) is expressed in epidermal basal keratinocyte (Martinsson H et al. 2005). During keratinocyte differentiation in epidermis, S100A7 redistributes to the cell periphery suggesting that S100A7 is released from differentiated keratinocytes (Broome AM et al. 2003; Ruse M et al. 2003). Extracellular S100A7 can act as an antibacterial agent restricting growth of E.coli (Glaser R et al. 2005). When purified from human cells the antimicrobial activity of S100A7 can be reversed by the addition of zinc suggesting that S100A7 may inhibit microbial growth through zinc chelation (Glaser R et al. 2005). Additionally, S100A7 has been reported to kill by permeabilizing bacterial membranes (Michalek M et al. 2009). The killing activity of S100A7 showed pH-dependent target specificity (Michalek M et al. 2009). At neutral pH, the Gram-negative bacterium E. coli was killed apparently without compromising its membrane, whereas at low pH exclusively the Gram-positive bacterium B. megaterium was killed by permeabilization of its cytoplasmic membrane (Michalek M et al. 2009).

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).

Literature References
PubMed ID Title Journal Year
10026247 Zinc-binding site of an S100 protein revealed. Two crystal structures of Ca2+-bound human psoriasin (S100A7) in the Zn2+-loaded and Zn2+-free states

Brodersen, DE, Nyborg, J, Kjeldgaard, M

Biochemistry 1999
22747601 Structural characterization of S100A15 reveals a novel zinc coordination site among S100 proteins and altered surface chemistry with functional implications for receptor binding

Murray, JI, Tonkin, ML, Whiting, AL, Peng, F, Farnell, B, Cullen, JT, Hof, F, Boulanger, MJ

BMC Struct. Biol. 2012
19810752 Identification and characterization of binding sites on S100A7, a participant in cancer and inflammation pathways

León, R, Murray, JI, Cragg, G, Farnell, B, West, NR, Pace, TC, Watson, PH, Bohne, C, Boulanger, MJ, Hof, F

Biochemistry 2009
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