Large-scale modelling of the divergent spectrin repeats in nesprins: giant modular proteins.

Nesprin-1 and nesprin-2 are nuclear envelope (NE) proteins characterized by a common structure of an SR (spectrin repeat) rod domain and a C-terminal transmembrane KASH [Klarsicht-ANC-Syne-homology] domain and display N-terminal actin-binding CH (calponin homology) domains. Mutations in these protei...

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Autores principales:	Flavia Autore, Mark Pfuhl, Xueping Quan, Aisling Williams, Roland G Roberts, Catherine M Shanahan, Franca Fraternali
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c4d82715b36b4818a5bfc3da7917e11c
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spelling	oai:doaj.org-article:c4d82715b36b4818a5bfc3da7917e11c2021-11-18T07:46:46ZLarge-scale modelling of the divergent spectrin repeats in nesprins: giant modular proteins.1932-620310.1371/journal.pone.0063633https://doaj.org/article/c4d82715b36b4818a5bfc3da7917e11c2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23671687/?tool=EBIhttps://doaj.org/toc/1932-6203Nesprin-1 and nesprin-2 are nuclear envelope (NE) proteins characterized by a common structure of an SR (spectrin repeat) rod domain and a C-terminal transmembrane KASH [Klarsicht-ANC-Syne-homology] domain and display N-terminal actin-binding CH (calponin homology) domains. Mutations in these proteins have been described in Emery-Dreifuss muscular dystrophy and attributed to disruptions of interactions at the NE with nesprins binding partners, lamin A/C and emerin. Evolutionary analysis of the rod domains of the nesprins has shown that they are almost entirely composed of unbroken SR-like structures. We present a bioinformatical approach to accurate definition of the boundaries of each SR by comparison with canonical SR structures, allowing for a large-scale homology modelling of the 74 nesprin-1 and 56 nesprin-2 SRs. The exposed and evolutionary conserved residues identify important pbs for protein-protein interactions that can guide tailored binding experiments. Most importantly, the bioinformatics analyses and the 3D models have been central to the design of selected constructs for protein expression. 1D NMR and CD spectra have been performed of the expressed SRs, showing a folded, stable, high content α-helical structure, typical of SRs. Molecular Dynamics simulations have been performed to study the structural and elastic properties of consecutive SRs, revealing insights in the mechanical properties adopted by these modules in the cell.Flavia AutoreMark PfuhlXueping QuanAisling WilliamsRoland G RobertsCatherine M ShanahanFranca FraternaliPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 5, p e63633 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Flavia Autore Mark Pfuhl Xueping Quan Aisling Williams Roland G Roberts Catherine M Shanahan Franca Fraternali Large-scale modelling of the divergent spectrin repeats in nesprins: giant modular proteins.
description	Nesprin-1 and nesprin-2 are nuclear envelope (NE) proteins characterized by a common structure of an SR (spectrin repeat) rod domain and a C-terminal transmembrane KASH [Klarsicht-ANC-Syne-homology] domain and display N-terminal actin-binding CH (calponin homology) domains. Mutations in these proteins have been described in Emery-Dreifuss muscular dystrophy and attributed to disruptions of interactions at the NE with nesprins binding partners, lamin A/C and emerin. Evolutionary analysis of the rod domains of the nesprins has shown that they are almost entirely composed of unbroken SR-like structures. We present a bioinformatical approach to accurate definition of the boundaries of each SR by comparison with canonical SR structures, allowing for a large-scale homology modelling of the 74 nesprin-1 and 56 nesprin-2 SRs. The exposed and evolutionary conserved residues identify important pbs for protein-protein interactions that can guide tailored binding experiments. Most importantly, the bioinformatics analyses and the 3D models have been central to the design of selected constructs for protein expression. 1D NMR and CD spectra have been performed of the expressed SRs, showing a folded, stable, high content α-helical structure, typical of SRs. Molecular Dynamics simulations have been performed to study the structural and elastic properties of consecutive SRs, revealing insights in the mechanical properties adopted by these modules in the cell.
format	article
author	Flavia Autore Mark Pfuhl Xueping Quan Aisling Williams Roland G Roberts Catherine M Shanahan Franca Fraternali
author_facet	Flavia Autore Mark Pfuhl Xueping Quan Aisling Williams Roland G Roberts Catherine M Shanahan Franca Fraternali
author_sort	Flavia Autore
title	Large-scale modelling of the divergent spectrin repeats in nesprins: giant modular proteins.
title_short	Large-scale modelling of the divergent spectrin repeats in nesprins: giant modular proteins.
title_full	Large-scale modelling of the divergent spectrin repeats in nesprins: giant modular proteins.
title_fullStr	Large-scale modelling of the divergent spectrin repeats in nesprins: giant modular proteins.
title_full_unstemmed	Large-scale modelling of the divergent spectrin repeats in nesprins: giant modular proteins.
title_sort	large-scale modelling of the divergent spectrin repeats in nesprins: giant modular proteins.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/c4d82715b36b4818a5bfc3da7917e11c
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Large-scale modelling of the divergent spectrin repeats in nesprins: giant modular proteins.

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