Database accession: MF7000612
Name: Murine S100A9 (C80A mutant) with Ca and Zn
PDB ID: 6zfe
Experimental method: X-ray (2.35 Å)
Assembly: Homodimer
Source organism: Mus musculus
Primary publication of the structure:
Signor L, Paris T, Mas C, Picard A, Lutfalla G, Boeri Erba E, Yatime L
Divalent cations influence the dimerization mode of murine S100A9 protein by modulating its disulfide bond pattern.
(2021) J. Struct. Biol. 213: 107689
PMID: 33359632
Abstract:
S100A9, with its congener S100A8, belongs to the S100 family of calcium-binding proteins found exclusively in vertebrates. These two proteins are major constituents of neutrophils. In response to a pathological condition, they can be released extracellularly and become alarmins that induce both pro- and anti-inflammatory signals, through specific cell surface receptors. They also act as antimicrobial agents, mainly as a S100A8/A9 heterocomplex, through metal sequestration. The mechanisms whereby divalent cations modulate the extracellular functions of S100A8 and S100A9 are still unclear. Importantly, it has been proposed that these ions may affect both the ternary and quaternary structure of these proteins, thereby influencing their physiological properties. In the present study, we report the crystal structures of WT and C80A murine S100A9 (mS100A9), determined at 1.45 and 2.35 Å resolution, respectively, in the presence of calcium and zinc. These structures reveal a canonical homodimeric form for the protein. They also unravel an intramolecular disulfide bridge that stabilizes the C-terminal tail in a rigid conformation, thus shaping a second Zn-binding site per S100A9 protomer. In solution, mS100A9 apparently binds only two zinc ions per homodimer, with an affinity in the micromolar range, and aggregates in the presence of excess zinc. Using mass spectrometry, we demonstrate that mS100A9 can form both non-covalent and covalent homodimers with distinct disulfide bond patterns. Interestingly, calcium and zinc seem to affect differentially the relative proportion of these forms. We discuss how the metal-dependent interconversion between mS100A9 homodimers may explain the versatility of physiological functions attributed to the protein.
Annotations from the GeneOntology database. Only terms that fit at least two of the interacting proteins are shown. Molecular function:
antioxidant activity antioxidant activity
calcium ion binding calcium ion binding
calcium-dependent protein binding calcium-dependent protein binding
Biological process:
actin cytoskeleton organization actin cytoskeleton organization
activation of cysteine-type endopeptidase activity involved in apoptotic process activation of cysteine-type endopeptidase activity involved in apoptotic process
antimicrobial humoral immune response mediated by antimicrobial peptide antimicrobial humoral immune response mediated by antimicrobial peptide
apoptotic process apoptotic process
astrocyte development astrocyte development
autocrine signaling autocrine signaling
autophagy autophagy
chronic inflammatory response chronic inflammatory response
endothelial cell migration endothelial cell migration
innate immune response innate immune response
leukocyte chemotaxis leukocyte chemotaxis
leukocyte migration involved in inflammatory response leukocyte migration involved in inflammatory response
neutrophil aggregation neutrophil aggregation
neutrophil chemotaxis neutrophil chemotaxis
peptide secretion peptide secretion
peptidyl-cysteine S-nitrosylation peptidyl-cysteine S-nitrosylation
positive regulation of blood coagulation positive regulation of blood coagulation
positive regulation of inflammatory response positive regulation of inflammatory response
positive regulation of intrinsic apoptotic signaling pathway positive regulation of intrinsic apoptotic signaling pathway
positive regulation of neuron projection development positive regulation of neuron projection development
positive regulation of peptide secretion positive regulation of peptide secretion
regulation of integrin biosynthetic process regulation of integrin biosynthetic process
regulation of respiratory burst involved in inflammatory response regulation of respiratory burst involved in inflammatory response
regulation of toll-like receptor signaling pathway regulation of toll-like receptor signaling pathway
regulation of translation regulation of translation
response to lipopolysaccharide response to lipopolysaccharide
Cellular component:
calprotectin complex calprotectin complex
cornified envelope cornified envelope
cytoplasm cytoplasm
cytoskeleton cytoskeleton
extracellular space extracellular space
S100A9 complex S100A9 complex
Structural annotations of the participating protein chains.Entry contents: 2 distinct polypeptide molecules
Chains: A, A-2
Notes: All chains according to the most probable oligomerization state stored in PDBe were considered.
Number of unique protein segments: 1
Name: Protein S100-A9
Source organism: Mus musculus
Length: 113 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMANKAPSQMERSITTIIDTFHQYSRKEGHPDTLSKKEFRQMVEAQLATFMKKEKRNEALINDIMEDLDTNQDNQLSFEECMMLMAKLIFACHEKLHENNPRGHGHSHGKGCGK
UniProtKB AC: P31725 (positions: 5-112)
Coverage: 95%
Name: Protein S100-A9
Source organism: Mus musculus
Length: 113 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMANKAPSQMERSITTIIDTFHQYSRKEGHPDTLSKKEFRQMVEAQLATFMKKEKRNEALINDIMEDLDTNQDNQLSFEECMMLMAKLIFACHEKLHENNPRGHGHSHGKGCGK
UniProtKB AC: P31725 (positions: 5-112)
Coverage: 95%
Evidence demonstrating that the participating proteins are unstructured prior to the interaction and their folding is coupled to binding. Representative domain in related structures: S-100/ICaBP type EF hand dimer
Evidence level: Direct evidence
Evidence coverage: The full structure participates in mutual synergistic folding.
Complex Evidence:
GuHCl-induced denaturation of the S100B protein dimer showed that it follows a two-state unfolding/refolding process (PMID:11888280). Other S100 proteins also showed two-state unfolding, no folded monomers were observed (PMID:18346834, PMID:18706914). The dimer has a globular and compact structure with the four helices in each subunit aligning to form a unicornate-type four-helix bundle (PMID:11790100). The hydrophobic core extends through the dimer interface.
Chain A:
N/A
Chain A-2:
N/A
Surface and contacts features:
Structures from the PDB that contain the same number of proteins, and the proteins from the two structures show a sufficient degree of pairwise similarity, i.e. they belong to the same UniRef90 cluster (the full proteins exhibit at least 90% sequence identity) and convey roughly the same region to their respective interactions (the two regions from the two proteins share a minimum of 70% overlap). Download the CIF file (.cif)
Download this entry's XML file (.xml)
Download this entry's JSON file (.json)
