Please use this identifier to cite or link to this item:
Title: Sortilin/Neurotensin Receptor 3: Three-dimensional Insights on its Coding Variants
Author: Coutinho, Maria Francisca
da Silva Santos, Liliana
Lacerda, Lúcia
Macedo-Ribeiro, Sandra
Prata, Maria João
Alves, Sandra
Keywords: Doenças Genéticas
Issue Date: Nov-2011
Publisher: Instituto Nacional de Saúde Doutor Ricardo Jorge, IP
Abstract: Introduction: Sortilin is a multifunctional sorting receptor required for Golgi-to-lysosome protein transport by a M-6-P independent pathway. It presents a unique structural organization with a 10-bladed β-propeller domain forming a tunnel where several ligands bind and is able to mediate the lysosomal targeting of sphingolipid activator proteins (SAPs), acid sphingomyelinase (AS) and cathepsins D and H. For some of these proteins no alternative receptor is known. The inner rim of the tunnel, along with several patches which function as additional binding sites have particularly high sequence conservation. Such structural organization is a key element for regulation of sortilin’s function and any sequence alterations changing it may potentially result in impaired lysosomal transport. As a result from the “1000Genomes Project”, several coding variants were identified for this protein with no known individuals carrying two of those variant alleles ever identified. Methods: In silico mutagenesis of sortilin was performed with SwissModelServer and the effect of each variant on its 3-dimensional structure was evaluated. The results were cross-linked with the potential pathogenicity predictions of PolyPhen and SIFT. Results/Discussion: Here we present the complete results of this in silico analysis, highlighting the potential of each one to disrupt sortilin’s structure and, consequently, impair its biological function and, ultimately, cause lysosomal storage and disease.
Peer review: yes
Appears in Collections:DGH - Posters/abstracts em congressos internacionais

Files in This Item:
File Description SizeFormat 
Coutinho, MF - SPDM2011.pdf1,86 MBAdobe PDFView/Open    Request a copy

FacebookTwitterDeliciousLinkedInDiggGoogle BookmarksMySpace
Formato BibTex MendeleyEndnote Degois 

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.