Disease relevance of S100A3

• The data showed modifications in the level of S100A3 protein expression; these modifications clearly identified the pilocytic astrocytomas from WHO grade II-IV astrocytic tumors as a distinct biological group [1].
• OBJECTIVES: To characterize the disordered epithelial elements of pilomatrixoma by localizing S100A2, S100A3 and S100A6 proteins [2].
• S100A3 mRNA expression displays an inverse correlation to breast cancer progression [3].

High impact information on S100A3

• The crystal structure of S100A3 allows the prediction of one putative Zn(2+) binding site in the C terminus of each subunit of S100A3 involving Cys and His residues in the coordination of the metal ion [4].
• S100A3 is a unique member of the EF-hand superfamily of Ca(2+)-binding proteins [4].
• This high affinity for Zn(2+) is attributed to the unusual high Cys content of S100A3 [4].
• Of the 10 Cys residues in S100A3, 5 only are free thiols, and accessible to 5,5'-dithiobis(2-nitro-benzoic acid); they display a high reactivity in the metal-free and Ca2+ form, but a 20-fold lowered reactivity in the Zn2+ form of S100A3 [5].
• Purification and cation binding properties of the recombinant human S100 calcium-binding protein A3, an EF-hand motif protein with high affinity for zinc [5].

Biological context of S100A3

• In contrast to the NMR structures, the EF-hand loops are well ordered in the apo-S100A3 crystal structure [6].
• We have characterized the subcellular distribution of S100A3, a cysteine-rich calcium binding protein, in human scalp hair shaft [7].
• Transfection of PLCB3 to neuroendocrine cell lines lacking expression suppresses the neoplastic phenotype and affects the gene expression of S100A3 and human mismatch repair protein, suggesting a role for PLCB3 in neuroendocrine tumorigenesis [8].

Anatomical context of S100A3

• The S100A3 antibody only stained the inner root sheath cuticle of some hair follicles but no melanocytes or melanocytic lesions [9].
• Aberrantly differentiated cells in benign pilomatrixoma reflect the normal hair follicle: immunohistochemical analysis of Ca-binding S100A2, S100A3 and S100A6 proteins [2].
• In the endocuticle, S100A3 was present on the inner portion of the endocuticle adjacent to the cell membrane complex, whereas hair keratins were present on the outer portion [7].
• In the hair shaft, S100A3 was primarily identified in the endocuticle and was also present in the intermacrofibrillar matrix surrounding macrofibril bundles of intermediate filament keratins in cortex cells [7].

Associations of S100A3 with chemical compounds

• Iodide replaces a water molecule at the surface of the S100A3 protein, whereas xenon binds in a hydrophobic cavity at the dimer interface [6].
• Metal-free S100A3, a cysteine-rich Ca(2+)- and Zn(2+)-binding protein, has been crystallized by vapour diffusion under the strict exclusion of oxygen and in the absence of divalent metal ions [6].
• Tandem mass spectrometry of the peptides resulting from endoproteinase digest of cuticle S100A3 revealed that the N-terminal methionine is replaced with an acetyl group [10].
• The transition metal ions Co2+, Zn2+ and Cd2+ were used as spectroscopic probes to investigate the role of the 10 cysteine residues per monomer S100A3 in metal binding [11].
• At the minimum concentration of thioglycolate required to elute S100A3 protein from the endocuticle into the reductive permanent waving lotion, enlarged delaminated cuticle fragments were observed [12].
• Gel filtration analyses showed that either enzymatic conversion of Arg-51 in S100A3 to citrulline or its mutational substitution with alanine (R51A) promotes a homotetramer assembly [13].

Other interactions of S100A3

• S100A1 and S100A3 antibodies are not expressed in melanocytic lesions and S100A2 is only found in selected tumours [9].
• In sharp contrast, the levels of expression of the S100A3 and S100A5 proteins differed markedly in the solid tumour tissue in relation to the astrocytic tumour types and grades [14].

Analytical, diagnostic and therapeutic context of S100A3

• The Zn(2+)-binding parameters of S100A3 were studied by equilibrium gel filtration and yielded a stoichiometry of four Zn2+ per monomer with a [Zn2+]0.5 of 11 microM and a Hill coefficient of 1.4 at physiological ionic strength [5].
• Fluorescence titrations with Ca2+ confirmed the very low affinity of S100A3 for this ion with a [Ca2+]0.5 of 30 mM and slight negative cooperativity [5].
• In situ hybridization revealed that the S100A3 gene was prominently expressed in cuticular cells of the hair follicle, and mRNA levels were highest in the keratogenous zone over the entire cuticular layer [15].
• The results of 2D gel electrophoresis showed that cuticle S100A3 has a slightly lower isoelectric point compared to the recombinant protein [10].
• Ultrastructural localization of S100A3, a cysteine-rich, calcium binding protein, in human scalp hair shafts revealed by rapid-freezing immunocytochemistry [7].

References