1. Cyclins Presentation1 Cyclin family of the yeast S. cerevisiae: Biological vs. Bioinformatical Presented by: Tzvika HoltzmanYan Tsitrin

2. Cyclins Presentation2 Cell Cycle Control S G2 M G1

3. Cyclins Presentation3 Cyclins levels during cell cycle Cln1,2 Clb5,6 Clb3,4 Clb1,2 G1SG2M Protein Levels

4. Cyclins Presentation4 S. cerevisiae cyclins and their CDKs

5. Cyclins Presentation5 Cyclin-CDK mode of action The cyclin uses the cyclin box to interact with its CDK

6. Cyclins Presentation6 Pho85 and its cyclins

7. Cyclins Presentation7 The project goal Using the yeast cyclins to compare biological and structural data to bioinformatical prediction and analysis The Nobel Prize in Physiology or Medicine 2001

8. Cyclins Presentation8 Cyclins clustering based on protein sequences Phylip ProtdistNatural Clb Cln

9. Cyclins Presentation9 Cln- family: cyclin boxes comparison (Clustalw + ESPript 2.0)

10. Cyclins Presentation10 Clb-family: cyclin boxes comparison (Clustalw + ESPript 2.0)

11. Cyclins Presentation11 Cyclins clustering based on domain sequences Natural Clb Cln Clb Phylip Protdist

12. Cyclins Presentation12 Cln family – 2D structure (PSIPRED V2.2) Cln1Cln 2 Cln3

13. Cyclins Presentation13 Clb family – 2D structure (PSIPRED V2.2) Clb1Clb2Clb3Clb4 Clb5Clb6

14. Cyclins Presentation14 CDK2-CyclinA complex Crystal structure of CDK2- CyclinA complex ( Jeffrey et al. Nature 376:313-320)

15. Cyclins Presentation15 Conclusions 1.The phylogenetic tree based on the whole protein can differ from the one that obtained from conserved domains. 2.The bioinformatical tools results should be analyzed according to biological context and they cannot disagree with biological facts.

16. Cyclins Presentation16 References Andrews et al., The cycline family of budding yeast: abundant use of a good idea Trends Genet. 14:66-72 Nasmyth, At the heart of the budding yeast cell cycle Trends Genet. 12:405-412 King et al., How proteolisys drives the cell cycle Science 274:1652- 1659 Carroll et al., Pho85 and signaling environmental conditions, Trends Biochem Sci. 27:87-93 Jeffrey et al., Mechanism of CDK activation revealed by the structure of a cyclinA-CDK2 complex, Nature 376:313-320

17. Cyclins Presentation17 Resources http://genome-www.stanford.edu/Saccharomyces/ - Saccharomyces Genome Databasehttp://genome-www.stanford.edu/Saccharomyces/ http://www.ncbi.nlm.nih.gov/BLAST - NCBI BLAST http://www.ebi.ac.uk/clustalw/ - multiple alignment, phylogenetic treehttp://www.ncbi.nlm.nih.gov/BLAST http://www.ebi.ac.uk/clustalw/ http://prodes.toulouse.inra.fr/ESPript/cgi-bin/nph-ESPript_exe.cgi - multiple alignmenthttp://prodes.toulouse.inra.fr/ESPript/cgi-bin/nph-ESPript_exe.cgi http://bioweb.pasteur.fr/seqanal/phylogeny/phylip-uk.html - Phylip programshttp://bioweb.pasteur.fr/seqanal/phylogeny/phylip-uk.html http://bioinf.cs.ucl.ac.uk/psipred/ - predict secondary structurehttp://bioinf.cs.ucl.ac.uk/psipred/ http://www.expasy.ch/tools/ - proteomic toolshttp://www.expasy.ch/tools/