General Information

Database accession: MF7000583

Name: Human migration inhibitory factor-related protein 8

PDB ID: 1mr8 PDBe

Experimental method: X-ray (1.90 Å)

Assembly: Homodimer

Source organism: Homo sapiens

Primary publication of the structure:

Ishikawa K, Nakagawa A, Tanaka I, Suzuki M, Nishihira J
The structure of human MRP8, a member of the S100 calcium-binding protein family, by MAD phasing at 1.9 A resolution.
(2000) Acta Crystallogr. D Biol. Crystallogr. 56: 559-66

PMID: 10771424 PubMed

Abstract:

The structure of human MRP8 in the calcium-bound form was determined at 1.9 A resolution by X-ray crystallography. The structure was initially solved by MAD phasing of an ytterbium-substituted crystal and was refined against data obtained from a Ca(2+)-bound crystal. The dimeric form of MRP8 was stabilized by hydrophobic interactions between mutually wrapped helices. There were two EF-hand motifs per monomer and each EF-hand bound one Ca(2+) with a different affinity [the affinity of the C-terminal EF-hand (EF-2) for Ca(2+) was stronger than that of the N-terminal EF-hand (EF-1)]. Furthermore, replacement with Yb(3+) occurred in the C-terminal EF-hand only, suggesting a more flexible nature for EF-2 than for EF-1. This, combined with previous observations that the helix in EF-2 (helix III) undergoes a large conformational change upon calcium binding, suggests that the C-terminal EF-hand (EF-2) plays a role as a trigger for Ca(2+)-induced conformational change.


Function and Biology Annotations from the GeneOntology database. Only terms that fit at least two of the interacting proteins are shown.

Molecular function:

arachidonic acid binding arachidonic acid binding GeneOntology

calcium ion binding calcium ion binding GeneOntology

calcium-dependent protein binding calcium-dependent protein binding GeneOntology

microtubule binding microtubule binding GeneOntology

RAGE receptor binding RAGE receptor binding GeneOntology

Toll-like receptor 4 binding Toll-like receptor 4 binding GeneOntology

zinc ion binding zinc ion binding GeneOntology

Biological process:

activation of cysteine-type endopeptidase activity involved in apoptotic process activation of cysteine-type endopeptidase activity involved in apoptotic process GeneOntology

apoptotic process apoptotic process GeneOntology

astrocyte development astrocyte development GeneOntology

autocrine signaling autocrine signaling GeneOntology

autophagy autophagy GeneOntology

chronic inflammatory response chronic inflammatory response GeneOntology

defense response to bacterium defense response to bacterium GeneOntology

defense response to fungus defense response to fungus GeneOntology

inflammatory response inflammatory response GeneOntology

innate immune response innate immune response GeneOntology

leukocyte migration involved in inflammatory response leukocyte migration involved in inflammatory response GeneOntology

neutrophil aggregation neutrophil aggregation GeneOntology

neutrophil chemotaxis neutrophil chemotaxis GeneOntology

peptide secretion peptide secretion GeneOntology

peptidyl-cysteine S-nitrosylation peptidyl-cysteine S-nitrosylation GeneOntology

positive regulation of cell growth positive regulation of cell growth GeneOntology

positive regulation of inflammatory response positive regulation of inflammatory response GeneOntology

positive regulation of intrinsic apoptotic signaling pathway positive regulation of intrinsic apoptotic signaling pathway GeneOntology

positive regulation of NF-kappaB transcription factor activity positive regulation of NF-kappaB transcription factor activity GeneOntology

positive regulation of peptide secretion positive regulation of peptide secretion GeneOntology

regulation of cytoskeleton organization regulation of cytoskeleton organization GeneOntology

regulation of toll-like receptor signaling pathway regulation of toll-like receptor signaling pathway GeneOntology

response to ethanol response to ethanol GeneOntology

response to lipopolysaccharide response to lipopolysaccharide GeneOntology

response to zinc ion response to zinc ion GeneOntology

sequestering of zinc ion sequestering of zinc ion GeneOntology

Cellular component:

calprotectin complex calprotectin complex GeneOntology

collagen-containing extracellular matrix collagen-containing extracellular matrix GeneOntology

cytoskeleton cytoskeleton GeneOntology

cytosol cytosol GeneOntology

extracellular exosome extracellular exosome GeneOntology

extracellular region extracellular region GeneOntology

extracellular space extracellular space GeneOntology

intermediate filament cytoskeleton intermediate filament cytoskeleton GeneOntology

nucleus nucleus GeneOntology

plasma membrane plasma membrane GeneOntology

secretory granule lumen secretory granule lumen GeneOntology

Structure Summary Structural annotations of the participating protein chains.

Entry contents: 2 distinct polypeptide molecules

Chains: A, B

Notes: All chains according to the most probable oligomerization state stored in PDBe were considered.

Number of unique protein segments: 1


Chain A

Name: Protein S100-A8

Source organism: Homo sapiens

Length: 93 residues

Sequence:Sequence according to the corresponding UniProt protein segmentMLTELEKALNSIIDVYHKYSLIKGNFHAVYRDDLKKLLETECPQYIRKKGADVWFKELDINTDGAVNFQEFLILVIKMGVAAHKKSHEESHKE

UniProtKB AC: P05109 (positions: 1-90) UniProt

Coverage: 96%

Chain B

Name: Protein S100-A8

Source organism: Homo sapiens

Length: 93 residues

Sequence:Sequence according to the corresponding UniProt protein segmentMLTELEKALNSIIDVYHKYSLIKGNFHAVYRDDLKKLLETECPQYIRKKGADVWFKELDINTDGAVNFQEFLILVIKMGVAAHKKSHEESHKE

UniProtKB AC: P05109 (positions: 1-90) UniProt

Coverage: 96%

Evidence 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 B:

N/A

Surface and contacts features:

Related Structure(s) 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).

There are 37 related structures in the MFIB database:






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