A computational model of the LGI1 protein suggests a common binding site for ADAM proteins.

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 me...

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Autores principales:	Emanuela Leonardi, Simonetta Andreazza, Stefano Vanin, Giorgia Busolin, Carlo Nobile, Silvio C E Tosatto
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c8b9b3cd58cc4a8ba3dd125b1188fd6f
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spelling	oai:doaj.org-article:c8b9b3cd58cc4a8ba3dd125b1188fd6f2021-11-18T06:56:35ZA computational model of the LGI1 protein suggests a common binding site for ADAM proteins.1932-620310.1371/journal.pone.0018142https://doaj.org/article/c8b9b3cd58cc4a8ba3dd125b1188fd6f2011-03-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21479274/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Mutations 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 β-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, by binding proteins at different times.The model was also used to predict effects of known disease-causing missense mutations. Most of the variants are predicted to alter protein folding while several other map to functional surface regions. In agreement with experimental evidence, this suggests that non-secreted LGI1 mutants could be retained within the cell by quality control mechanisms or by altering interactions required for the secretion process.Emanuela LeonardiSimonetta AndreazzaStefano VaninGiorgia BusolinCarlo NobileSilvio C E TosattoPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 3, p e18142 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Emanuela Leonardi Simonetta Andreazza Stefano Vanin Giorgia Busolin Carlo Nobile Silvio C E Tosatto A computational model of the LGI1 protein suggests a common binding site for ADAM proteins.
description	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 β-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, by binding proteins at different times.The model was also used to predict effects of known disease-causing missense mutations. Most of the variants are predicted to alter protein folding while several other map to functional surface regions. In agreement with experimental evidence, this suggests that non-secreted LGI1 mutants could be retained within the cell by quality control mechanisms or by altering interactions required for the secretion process.
format	article
author	Emanuela Leonardi Simonetta Andreazza Stefano Vanin Giorgia Busolin Carlo Nobile Silvio C E Tosatto
author_facet	Emanuela Leonardi Simonetta Andreazza Stefano Vanin Giorgia Busolin Carlo Nobile Silvio C E Tosatto
author_sort	Emanuela Leonardi
title	A computational model of the LGI1 protein suggests a common binding site for ADAM proteins.
title_short	A computational model of the LGI1 protein suggests a common binding site for ADAM proteins.
title_full	A computational model of the LGI1 protein suggests a common binding site for ADAM proteins.
title_fullStr	A computational model of the LGI1 protein suggests a common binding site for ADAM proteins.
title_full_unstemmed	A computational model of the LGI1 protein suggests a common binding site for ADAM proteins.
title_sort	computational model of the lgi1 protein suggests a common binding site for adam proteins.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/c8b9b3cd58cc4a8ba3dd125b1188fd6f
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A computational model of the LGI1 protein suggests a common binding site for ADAM proteins.

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