2. RhoGTPases and Actin Cytoskeleton Alex André Andres Elena Isabelle Shuoshuo Structural & Functional Predictions for ELMO homologues A Bioinformatic Approach

3. Overview Actin cytoskeleton  Cytoskeletal dynamics in cellular processes  Rho GTPases play role in cytoskeletal remodeling  GEFs and GAPs regulate Rho GTPases  ELMO1 – GEF for Rac

4. ELMO1 (Engulfment and cell motility protein 1)  CED12 in C.elegans phagocytosis of apoptotic cells and cell motility  Not much known (19 papers in Pubmed)  What shall we do? BIOINFORMATICS

5. ELMO1 domain organisation

6. Alignment of the ELMO-domain

7. Alignment of the PH-domain

8. Phylogenetic relationship of ELMO1 homologues insects yeasts vertebrates plants Nematodes 100 64 100

9. Biocomputing and Reality

10. Prediction of phosphorylation sites in the ELMO1 sequence AKT1 Rac-alpha S/T kinase Hck haematopoetic cell kinase

11. Structure prediction of PH domain by homology remodelling PH domain identity Geno3D Sequence Identity 23.6% 3 models were predicted by homology modelling

12. Proper homology modelling can yield significantly more information than conventional analysis

13. side view overhead view

14. The ELMO team

15. “Critiques help us to progress”