Database accession: MF7000609
Name: Human S100A1 protein (mutant)
PDB ID: 2lp2
Experimental method: NMR
Assembly: Homodimer
Source organism: Homo sapiens
Primary publication of the structure:
Nowakowski M, Ruszczyńska-Bartnik K, Budzińska M, Jaremko L, Jaremko M, Zdanowski K, Bierzyński A, Ejchart A
Impact of calcium binding and thionylation of S100A1 protein on its nuclear magnetic resonance-derived structure and backbone dynamics.
(2013) Biochemistry 52: 1149-59
PMID: 23351007
Abstract:
S100 proteins play a crucial role in multiple important biological processes in vertebrate organisms acting predominantly as calcium signal transmitters. S100A1 is a typical representative of this family of proteins. After four Ca(2+) ions bind, it undergoes a dramatic conformational change, resulting in exposure, in each of its two identical subunits, a large hydrophobic cleft that binds to target proteins. It has been shown that abnormal expression of S100A1 is strongly correlated with a number of severe human diseases: cardiomyopathy and neurodegenerative disorders. A few years ago, we found that thionylation of Cys 85, the unique cysteine in two identical S100A1 subunits, leads to a drastic increase of the affinity of the protein for calcium. We postulated that the protein activated by thionylation becomes a more efficient calcium signal transmitter. Therefore, we decided to undertake, using nuclear magnetic resonance methods, a comparative study of the structure and dynamics of native and thionylated human S100A1 in its apo and holo states. In this paper, we present the results obtained for both forms of this protein in its holo state and compare them with the previously published structure of native apo-S100. The main conclusion that we draw from these results is that the increased calcium binding affinity of S100A1 upon thionylation arises, most probably, from rearrangement of the hydrophobic core in its apo form.
Annotations from the GeneOntology database. Only terms that fit at least two of the interacting proteins are shown. Molecular function:
ATPase binding ATPase binding
calcium ion binding calcium ion binding
calcium-dependent protein binding calcium-dependent protein binding
identical protein binding identical protein binding
protein homodimerization activity protein homodimerization activity
S100 protein binding S100 protein binding
Biological process:
intracellular signal transduction intracellular signal transduction
positive regulation of nitric-oxide synthase activity positive regulation of nitric-oxide synthase activity
positive regulation of sprouting angiogenesis positive regulation of sprouting angiogenesis
regulation of heart contraction regulation of heart contraction
substantia nigra development substantia nigra development
Cellular component:
cytoplasm cytoplasm
cytosol cytosol
extracellular region extracellular region
Golgi apparatus Golgi apparatus
mitochondrion mitochondrion
nucleoplasm nucleoplasm
nucleus nucleus
protein-containing complex protein-containing complex
sarcoplasmic reticulum sarcoplasmic reticulum
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
Name: Protein S100-A1
Source organism: Homo sapiens
Length: 94 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMGSELETAMETLINVFHAHSGKEGDKYKLSKKELKELLQTELSGFLDAQKDVDAVDKVMKELDENGDGEVDFQEYVVLVAALTVACNNFFWENS
UniProtKB AC: P23297 (positions: 2-94)
Coverage: 98%
Name: Protein S100-A1
Source organism: Homo sapiens
Length: 94 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMGSELETAMETLINVFHAHSGKEGDKYKLSKKELKELLQTELSGFLDAQKDVDAVDKVMKELDENGDGEVDFQEYVVLVAALTVACNNFFWENS
UniProtKB AC: P23297 (positions: 2-94)
Coverage: 98%
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:
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)
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