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RhoGTPases and Actin Cytoskeleton

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

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

  3. 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

  4. ELMO1 domain organisation

  5. Alignment of the ELMO-domain

  6. Alignment of the PH-domain

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

  8. Biocomputing and Reality

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

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

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

  12. side view overhead view

  13. The ELMO team

  14. “Critiques help us to progress”