a computational model of the lgi1 protein suggests a common binding site for adam proteinslgi1蛋白质的计算模型得出了一个共同的结合位点为亚当的蛋白质.pdfVIP

A Computational Model of the LGI1 Protein Suggests a Common Binding Site for ADAM Proteins 1 1 1,2 3 3 Emanuela Leonardi , Simonetta Andreazza , Stefano Vanin , Giorgia Busolin , Carlo Nobile , Silvio C. E. Tosatto1* 1 Department of Biology, University of Padova, Padova, Italy, 2 School of Applied Science, University of Huddersfield, Huddersfield, United Kingdom, 3 Institute of Neurosciences, Consiglio Nazionale delle Ricerche (CNR), Padova, Italy Abstract Mutations of human leucine-rich glioma inactivated (LGI1) gene encoding the epitempin protein cause autosomal dominant temporal lateral epilepsy (ADTLE), a rare familial partial epileptic syndrome. The LGI1 gene seems to have a role on the transmission of neuronal messages but the exact molecular mechanism remains unclear. In contrast to other genes involved in epileptic disorders, epitempin shows no homology with known ion channel genes but contains two domains, composed of repeated structural units, known to mediate protein-protein interactions. A three dimensional in silico model of the two epitempin domains was built to predict the structure-function relationship and propose a functional model integrating previous experimental findings. Conserved and electrostatic charged regions of the model surface suggest a possible arrangement between the two domains and identifies a possible ADAM protein binding site in the b-propeller domain and another protein binding site in the leucine-rich repeat domain. The functional model indicates that epitempin could mediate the interaction between proteins localized to different synaptic sides in a static way, by forming a dimer, or in a dynamic way,