RhoGTPases and Actin Cytoskeleton

Alex

André

Andres

Elena

Isabelle

Shuoshuo

Structural & FunctionalPredictions for

ELMO homologues A Bioinformatic Approach

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

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

ELMO1 domain organisation

Alignment of the ELMO-domain

Alignment of the PH-domain

Phylogenetic relationship of ELMO1 homologues

insects

yeasts

vertebratesvertebratesvertebratesvertebratesvertebrates

plants

Nematodes

100100

100

100

64

100

100

Biocomputing and Reality

Prediction of phosphorylation sites in the ELMO1 sequence

AKT1 Rac-alpha S/T kinase Hck haematopoetic cell kinase

Structure prediction of PH domain by homology remodelling

PH domain identity Geno3D Sequence Identity 23.6%3 models were predicted by homology modelling

Proper homology modelling can yield significantly more information than

conventional analysis

side view overhead view

The ELMO team

“Critiques help us to progress”