RhoGTPases and Actin Cytoskeleton

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
insects
100
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