Investigation of interaction between EML1 and Microtubules
1 Koç University
The EML1 protein, which is a member of the EML (Echinoderm Microtubule-Associated Protein-Like) family, plays a role in the early development of the brain. It has three important structural features. The first is a trimerization domain (TD) at the N-terminus that helps form functional trimers, which are necessary for the protein’s interaction with microtubules. Secondly, it contains a TAPE (tandem atypical propeller in EMLs) domain, comprised of a pair of beta-propellers, one of which contains an atypical blade distinct from WD40 repeats. This domain is likely involved in binding tubulin. Thirdly, it harbours a HELP motif, which is not a separate domain but serves as an integral part of the hydrophobic core that links the two beta-propellers in the TAPE domain. Cortical heterotopias are mainly caused by mutations in genes associated with cytoskeletal elements and microtubule function. The T243A mutation in the EML1 protein’s HELP motif has been shown to cause severe subcortical heterotopia in both human and mouse models. However, it is not yet clear exactly how this mutation affects its function and interaction with microtubules. We aim to determine the mutation’s effect on protein structure and interactions with microtubules which would provide insight into the pathogenesis of the heterotopia and other microtubule-associated disorders and investigate the interaction between the EML1 protein and microtubules during cell division through advanced microscopy and proteomic techniques.