S100 calcium-binding protein A1

S100 calcium binding protein A1

PDB rendering based on 1k2h.
Identifiers
Symbols S100A1; S100; S100-alpha; S100A
External IDs OMIM: 176940 MGI: 1338917 HomoloGene: 4566 GeneCards: S100A1 Gene
RNA expression pattern
More reference expression data
Orthologs
Species Human Mouse
Entrez 6271 20193
Ensembl ENSG00000160678 ENSMUSG00000044080
UniProt P23297 Q91V77
RefSeq (mRNA) NM_006271 NM_011309.3
RefSeq (protein) NP_006262 NP_035439.1
Location (UCSC) Chr 1:
153.6 – 153.6 Mb		 Chr 3:
90.31 – 90.32 Mb
PubMed search [1] [2]

S100 calcium-binding protein A1, also known as S100A1, is a protein which in humans is encoded by the S100A1 gene.[1][2]

Contents

Function

The protein encoded by this gene is a member of the S100 family of proteins containing 2 EF-hand calcium-binding motifs.[3] S100 proteins are localized in the cytoplasm and/or nucleus of a wide range of cells, and involved in the regulation of a number of cellular processes such as cell cycle progression and differentiation. S100 genes include at least 13 members which are located as a cluster on chromosome 1q21. This protein may function in stimulation of Ca2+-induced Ca2+ release, inhibition of microtubule assembly, and inhibition of protein kinase C-mediated phosphorylation. Reduced expression of this protein has been implicated in cardiomyopathies.[1]

S100A1 overexpression enhances cardiac contractile performance which suggests that S100A1 is a regulator of myocardial contractility. S100A1 improves cardiac performance both by regulating calcium ion handling by the sarcoplasmic reticulum and the responsiveness of myofibrils to calcium ion.[4]

In melanocytic cells, S100A1 gene expression may be regulated by MITF.[5]

S100A1 structure

Like many other S100 proteins, S100A1 can exist as either a hetero or homodimer. Protein nuclear magnetic resonance spectroscopy structural information on the homodimeric form of this protein shows that each monomer is quite helical, and contains two EF-hand calcium-binding loops; an 'S100' EF hand in the N-terminus and a canonical EF-hand in the C-terminus. These domains are linked by a 'hinge' region, which exists as a random coil. Both EF-hands bind calcium, although the real EF-hand has a significantly higher affinity (with a dissociation constant of roughly 20 micromolar). The two calcium-binding regions neighbor each other in three dimensional space, and are connected to each other through a short beta sheet region (residues 27–29 and 68–70).

The S100A1 homodimer is high affinity (nanomolar range or tighter), and is formed through hydrophobic packing of an X-type 4-helix bundle created between helices 1, 1', 4, and 4'.

Recently the most accurate high-resolution solution structure of human apo-S100A1 protein (PDB accesion code: 2L0P) has been determined by means of NMR spectroscopy (ref. Nowakowski, M., Jaremko, L., Jaremko, M., Zhukov, I., Belczyk, A., Bierzynski, A,. Ejchart, A. Solution NMR structure and dynamics of human apo-S100A1 protein., J. Struct. Biol. 2011, 174, 391-399, doi: 10.1016/j.jsb.2011.01.011).

Conformational change

Upon binding calcium, helix 3 of S100A1 (and most other S100 proteins as well) re-orients from being relatively antiparallel to helix 4 to being roughly perpendicular. This conformational change is different from most EF-hands, in that the entering helix, and not the exiting helix, moves. This conformational change exposes a large hydrophobic pocket between helix 3, 4, and the 'hinge' region of S100A1 that is involved in virtually all calcium-dependent target protein interactions. These biophysical properties seem to be well conserved across the S100 family of proteins. Helix 3, 4, and the hinge region are the most divergent areas between individual S100 proteins, and so it is likely that the sequence of these regions is pivotal in fine-tuning calcium-dependent target binding by S100 proteins.

Interactions

S100 calcium-binding protein A1 has been shown to interact with PGM1,[6] S100B[7][8][9] and S100A4.[7][10]

References

  1. ^ a b "Entrez Gene: S100A1 S100 calcium binding protein A1". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=6271. 
  2. ^ Morii K, Tanaka R, Takahashi Y, Minoshima S, Fukuyama R, Shimizu N, Kuwano R (February 1991). "Structure and chromosome assignment of human S100 alpha and beta subunit genes". Biochem. Biophys. Res. Commun. 175 (1): 185–91. doi:10.1016/S0006-291X(05)81218-5. PMID 1998503. 
  3. ^ Marenholz I, Heizmann CW, Fritz G (October 2004). "S100 proteins in mouse and man: from evolution to function and pathology (including an update of the nomenclature)". Biochem. Biophys. Res. Commun. 322 (4): 1111–22. doi:10.1016/j.bbrc.2004.07.096. PMID 15336958. 
  4. ^ Most P, Bernotat J, Ehlermann P, Pleger ST, Reppel M, Börries M, Niroomand F, Pieske B, Janssen PM, Eschenhagen T, Karczewski P, Smith GL, Koch WJ, Katus HA, Remppis A (November 2001). "S100A1: a regulator of myocardial contractility". Proc. Natl. Acad. Sci. U.S.A. 98 (24): 13889–94. doi:10.1073/pnas.241393598. PMC 61137. PMID 11717446. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=61137. 
  5. ^ Hoek KS, Schlegel NC, Eichhoff OM, et al. (2008). "Novel MITF targets identified using a two-step DNA microarray strategy". Pigment Cell Melanoma Res. 21 (6): 665–76. doi:10.1111/j.1755-148X.2008.00505.x. PMID 19067971. 
  6. ^ Landar, A; Caddell G, Chessher J, Zimmer D B (Sep. 1996). "Identification of an S100A1/S100B target protein: phosphoglucomutase". Cell Calcium (SCOTLAND) 20 (3): 279–85. doi:10.1016/S0143-4160(96)90033-0. ISSN 0143-4160. PMID 8894274. 
  7. ^ a b Rual, Jean-François; Venkatesan Kavitha, Hao Tong, Hirozane-Kishikawa Tomoko, Dricot Amélie, Li Ning, Berriz Gabriel F, Gibbons Francis D, Dreze Matija, Ayivi-Guedehoussou Nono, Klitgord Niels, Simon Christophe, Boxem Mike, Milstein Stuart, Rosenberg Jennifer, Goldberg Debra S, Zhang Lan V, Wong Sharyl L, Franklin Giovanni, Li Siming, Albala Joanna S, Lim Janghoo, Fraughton Carlene, Llamosas Estelle, Cevik Sebiha, Bex Camille, Lamesch Philippe, Sikorski Robert S, Vandenhaute Jean, Zoghbi Huda Y, Smolyar Alex, Bosak Stephanie, Sequerra Reynaldo, Doucette-Stamm Lynn, Cusick Michael E, Hill David E, Roth Frederick P, Vidal Marc (Oct. 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature (England) 437 (7062): 1173–8. doi:10.1038/nature04209. PMID 16189514. 
  8. ^ Deloulme, J C; Assard N, Mbele G O, Mangin C, Kuwano R, Baudier J (Nov. 2000). "S100A6 and S100A11 are specific targets of the calcium- and zinc-binding S100B protein in vivo". J. Biol. Chem. (UNITED STATES) 275 (45): 35302–10. doi:10.1074/jbc.M003943200. ISSN 0021-9258. PMID 10913138. 
  9. ^ Yang, Q; O'Hanlon D, Heizmann C W, Marks A (Feb. 1999). "Demonstration of heterodimer formation between S100B and S100A6 in the yeast two-hybrid system and human melanoma". Exp. Cell Res. (UNITED STATES) 246 (2): 501–9. doi:10.1006/excr.1998.4314. ISSN 0014-4827. PMID 9925766. 
  10. ^ Wang, G; Rudland P S, White M R, Barraclough R (Apr. 2000). "Interaction in vivo and in vitro of the metastasis-inducing S100 protein, S100A4 (p9Ka) with S100A1". J. Biol. Chem. (UNITED STATES) 275 (15): 11141–6. doi:10.1074/jbc.275.15.11141. ISSN 0021-9258. PMID 10753920. 


Both through biochemical and cell culture assays, S100A1 has also been shown to interact with the calmodulin binding region of the ryanodine receptor (RyR), as well as the regulatory subunit of PKA IIb. In addition, multiple drugs, including Pentamidine, Amlexanox, Olopatadine, Cromolyn, and Propanolol, are known to bind to S100A1, although their affinities are often in the mid-micromolar range.

Further reading

  • Zimmer DB, Cornwall EH, Landar A, Song W (1995). "The S100 protein family: history, function, and expression.". Brain Res. Bull. 37 (4): 417–29. PMID 7620916. 
  • Schäfer BW, Heizmann CW (1996). "The S100 family of EF-hand calcium-binding proteins: functions and pathology.". Trends Biochem. Sci. 21 (4): 134–40. PMID 8701470. 
  • Garbuglia M, Verzini M, Sorci G, et al. (2000). "The calcium-modulated proteins, S100A1 and S100B, as potential regulators of the dynamics of type III intermediate filaments.". Braz. J. Med. Biol. Res. 32 (10): 1177–85. PMID 10510252. 
  • Engelkamp D, Schäfer BW, Erne P, Heizmann CW (1992). "S100 alpha, CAPL, and CACY: molecular cloning and expression analysis of three calcium-binding proteins from human heart.". Biochemistry 31 (42): 10258–64. doi:10.1021/bi00157a012. PMID 1384693. 
  • Morii K, Tanaka R, Takahashi Y, et al. (1991). "Structure and chromosome assignment of human S100 alpha and beta subunit genes.". Biochem. Biophys. Res. Commun. 175 (1): 185–91. doi:10.1016/S0006-291X(05)81218-5. PMID 1998503. 
  • Baudier J, Glasser N, Gerard D (1986). "Ions binding to S100 proteins. I. Calcium- and zinc-binding properties of bovine brain S100 alpha alpha, S100a (alpha beta), and S100b (beta beta) protein: Zn2+ regulates Ca2+ binding on S100b protein.". J. Biol. Chem. 261 (18): 8192–203. PMID 3722149. 
  • Kato K, Kimura S (1985). "S100ao (alpha alpha) protein is mainly located in the heart and striated muscles.". Biochim. Biophys. Acta 842 (2–3): 146–50. PMID 4052452. 
  • Schäfer BW, Wicki R, Engelkamp D, et al. (1995). "Isolation of a YAC clone covering a cluster of nine S100 genes on human chromosome 1q21: rationale for a new nomenclature of the S100 calcium-binding protein family.". Genomics 25 (3): 638–43. doi:10.1016/0888-7543(95)80005-7. PMID 7759097. 
  • Engelkamp D, Schäfer BW, Mattei MG, et al. (1993). "Six S100 genes are clustered on human chromosome 1q21: identification of two genes coding for the two previously unreported calcium-binding proteins S100D and S100E.". Proc. Natl. Acad. Sci. U.S.A. 90 (14): 6547–51. doi:10.1073/pnas.90.14.6547. PMC 46969. PMID 8341667. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=46969. 
  • Garbuglia M, Verzini M, Giambanco I, et al. (1996). "Effects of calcium-binding proteins (S-100a(o), S-100a, S-100b) on desmin assembly in vitro.". FASEB J. 10 (2): 317–24. PMID 8641565. 
  • Landar A, Caddell G, Chessher J, Zimmer DB (1997). "Identification of an S100A1/S100B target protein: phosphoglucomutase.". Cell Calcium 20 (3): 279–85. doi:10.1016/S0143-4160(96)90033-0. PMID 8894274. 
  • Remppis A, Greten T, Schäfer BW, et al. (1996). "Altered expression of the Ca(2+)-binding protein S100A1 in human cardiomyopathy.". Biochim. Biophys. Acta 1313 (3): 253–7. PMID 8898862. 
  • Treves S, Scutari E, Robert M, et al. (1997). "Interaction of S100A1 with the Ca2+ release channel (ryanodine receptor) of skeletal muscle.". Biochemistry 36 (38): 11496–503. doi:10.1021/bi970160w. PMID 9298970. 
  • Groves P, Finn BE, Kuźnicki J, Forsén S (1998). "A model for target protein binding to calcium-activated S100 dimers.". FEBS Lett. 421 (3): 175–9. doi:10.1016/S0014-5793(97)01535-4. PMID 9468301. 
  • Mandinova A, Atar D, Schäfer BW, et al. (1998). "Distinct subcellular localization of calcium binding S100 proteins in human smooth muscle cells and their relocation in response to rises in intracellular calcium.". J. Cell. Sci. 111 ( Pt 14): 2043–54. PMID 9645951. 
  • Osterloh D, Ivanenkov VV, Gerke V (1999). "Hydrophobic residues in the C-terminal region of S100A1 are essential for target protein binding but not for dimerization.". Cell Calcium 24 (2): 137–51. doi:10.1016/S0143-4160(98)90081-1. PMID 9803314. 
  • Garbuglia M, Verzini M, Donato R (1999). "Annexin VI binds S100A1 and S100B and blocks the ability of S100A1 and S100B to inhibit desmin and GFAP assemblies into intermediate filaments.". Cell Calcium 24 (3): 177–91. doi:10.1016/S0143-4160(98)90127-0. PMID 9883272. 
  • Ridinger K, Ilg EC, Niggli FK, et al. (1999). "Clustered organization of S100 genes in human and mouse.". Biochim. Biophys. Acta 1448 (2): 254–63. PMID 9920416.