proteins, what are they really? 1.A little bit about the family 2.Where they are found 3.Structure 4.Cell Apoptosis 5.Nerve cells 6.Nerve cell degeneration 7.The future of

A little bit about the family 30kDa acidic proteins 70% of the proteins is conserved on the amino acid level Each monomer is denoted by a Greek character: β, γ, ε, ζ, η, σ, and τ In vivo they form homo and heterodimers Phosphoryalted or nonphosphorylated?

These proteins make up 1% of all the soluble proteins in the brain ε is expressed in the spermatogonia and ζ is expressed in primary and secondary spermatocytes σ is found in the epithelial cells that are part of the dermal layer of the tongue. Where proteins are found

Structure

S136

Apoptosis R18 BAD Bcl-2 Bcl-X Cell Death

Nerve cells: Serotonin N- Acetyltransferase Complex AANAT is an enzyme that controls the biological clock. Research has found that ζ binds with AANAT, which enhances the affinity for AANAT to bind with other substrates. Energy measurements were made after ζ bound with AANAT and then bound with acetyl- Co-A. In terms of Gibbs free energy, it bound with a ΔG of ~0.8 kcal/mol, as opposed to the large negative values with just AANAT by itself.

 :Serotonin N-Acetyltransferase Complex

Nerve Cells: Parathyroid hormone receptor It has been researched the C-terminal tail of PTHR has been identified as RSGSSSYS this strongly correlates with the binding motif of RSXpSXP. Two binding sites on PTHR for It is hypothesized proteins may act as mediators between steroids and PTHR. This also could have effects on calcium regulation; the exact function of the binding is undetermined.

Neurodegenerative disease: Kainic acid (Ka) In rats the build up of Kainic acid (Ka), a neurotoxin, induces the expression of ζ mRNA. Up regulation of ζ and p53 The association with p53 for this experiment may suggest that ζ may be a mediator to this type of cell death. It is hypothesized when ζ binds to p53 it may change its affinity to bind with DNA sequences.

Neurodegenerative disease: Spinocerebellar Ataxia type 1 (SCA1) A neurodegenerative disease that is caused by an unusual long polyglutamine track, 82Q, in the ataxin-1 protein. In vivo Akt phosphorylates S776 on mutant ataxin 1 this allows for binding. By binding ataxin 1 to mutant ataxin 1 becomes more toxic to nerve cells because neurdegeneration cannot occur, this causes a build up of mutant ataxin 1and causes degeneration of nerve cells. the longer the polyglutamine track the greater the binding affinity for isotypes.

Neurodegenerative disease: Multiple system atrophy (MSA) This disease causes glial cytoplasmic inclusions (GCI), which are aggregates of α-synulein, found in the nucleus and the presynaptic the cell bodies of oligodendrites and Lewy bodies One major component of the GCIs is α-synuclein, 140 amino acids long. α-synuclein can bind to by the phosphorylation S129. It is hypothesized that in MSA may mediate the interaction between α-synuclein and protein kinase C (PKC). This means that would be a possible cofactor for GCI formation.

J.E Galvin, “Glial Cytoplasmic Inculsions”

The future of In E. tenella proteins are used in a mannitol cell cycle pathway, this is believed to be a part of the sporulation process. A major enzyme in the pathway is mannitol-1-phosphate dehydrogenase (M1PD) Sm14-3-3—1 Sm14-3-3—1 interacts with a phosphorylated s. mansoni receptor kinase-1domian, which is homologous to the mammalian transforming growth factor β receptor-1 (TGFβ) 26 to 45% effective in preventing in mice infected with S. mansoni

For Further Reading: [1] M.B. Yaffe, How do proteins work? Gatekeeper phosphorylation and the molecular anvil hypothesis. FEBS Lett. 513 (2002), pp. 53– 57. [2] H. Fu, R.R. Subramanian, S.C Masters, Proteins: Structure, Function, and Regulation. Annu. Rev. Pharmacol. Toxicol 40 (2000), pp [3] T. Obsil, “Structural Biology of protiens” (2001) [4] M.B Yaffe, A.E.H. Elia, Phosphoserine/threonine-binding domains. Curr. Opin. Cell Biol. 2 (2001), pp [5] H. Yang, S.C. Masters, H. Wang and H. Fu. Biochim. Biophys. Acta 1547 (2001), pp. 313–319. [6] H. Ibelgaufts “COPE: Apoptosis” (2003) [7] R.R. Subramanian, S.C. Masters, H. Zhang and H. Fu. Exp. Cell Res. 271 (2001), pp. 142–151. [8] M. Adachi, Y.B. Zhang, K. Imai, Mutation of BAD with in the BH3 domain impairs its phosphorylation-mediated regulation. FEBS lett. 551 (2003), pp [9] S.C. Masters, H. Fu, Proteins Mediate an Essential Anti-apoptotic Signal. J. Biol. Chem. 276 (2001), pp [10] A.J. Muslin and H. Xing, proteins: regulation of subcellular localization by molecular interference. Cell. Signal. 19 (2000), pp. 703– 709. [11] K. Toyooka et al., Isolation and the structure of the mouse η chain gene and the distribution of η mRNA in the mouse brain. Mole. Brain Res. 100 (2002) pp [12] H. Tazawa, S. Takahashi, J. Zilliacus, Interaction of the parathyroid hormone receptor with the protien. Biochim. Biophys. Acta 160 (2003) pp [13] T. Obsil, R. Ghirlando, D.C. Klein, S. Gangly, F. Dyda, Crystal Structure of the ζ: Serotonin N-Acetyltransferase Complex: A Role for Scaffolding in Enzyme Regulation. Cell. 105 (2001), pp [14] T. Komori, K. Ishizawa, N. Arai, Immunoexpression of proteins in glial cytoplasmic inclusions of multiple system atrophy. Acta Neuropath. 106 (2003) pp [15] M.P. Brug, S. Goodenough, P. Wilce, Kainic acid induces ζ expression in distinct regions of rat brain. Brain Res. 956 (2002) pp [16] X. Monatano, Correspondence: Common amino acid motifs in p53, and Akt protein families. FEBS Lett. 507 (2001), pp [17] H.K. Chen et al., Interaction of Akt-Phosphorylated Ataxin-1 with Mediates Neurodegeneration in Spinocerebellar Ataxia Type-1. Cell 113 (2003), pp [18] K.K. Dev, K. Hofele, S. Barbieri, V.L. Buchman, H. Putten, Part II: α-synuclein and its molecular pathophysiological role in neurodegenerative disease. Neuropharm. 45 (2003) pp [19] M.M. Siles-Lucas, B. Gottstein, The protein: a key molecule in parasites as in other organisms. Tren. Parasite. 12 (2003) pp [20] D. Schectman et al., The protein as a vaccine candidate against schistosomiasis. Parasite Immunol. 23 (2001), pp [21] J.E Galvin, “Glial Cytoplasmic Inculsions”. (2000) [22] H. Ibelgaufts “COPE: Raf” (2002)