Sequential and structural determinants of protein aggregation

The project entitled "Sequential and structural determinants of protein aggregation" aims to study the factors that control protein deposition but also tries to develop new strategies to facilitate its comprehension. <br/>Protein aggregation is related with an increasing number of hu...

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Autor: Sánchez de Groot, Natalia
Tipo de recurso: tesis doctoral
Estado:Versión publicada
Fecha de publicación:2010
País:España
Institución:CBUC, CESCA
Repositorio:TDR. Tesis Doctorales en Red
OAI Identifier:oai:www.tdx.cat:10803/3625
Acceso en línea:http://www.tdx.cat/TDX-1222110-184311
http://hdl.handle.net/10803/3625
Access Level:acceso abierto
Palabra clave:E.Coli
Agregació
Proteïna
Ciències Experimentals
57
577
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spelling Sequential and structural determinants of protein aggregationSánchez de Groot, NataliaE.ColiAgregacióProteïnaCiències Experimentals57577The project entitled "Sequential and structural determinants of protein aggregation" aims to study the factors that control protein deposition but also tries to develop new strategies to facilitate its comprehension. <br/>Protein aggregation is related with an increasing number of human disorders such as Alzheimer's disease, Parkinson disease or type II diabetes. Understanding the determinants that modulate the deposition process is a necessary step to develop new strategies to tackle these debilitating pathologies. Additionally, the accumulation of heterologous protein as intracellular aggregates during recombinant expression represents one of the main problems in down stream processing. Accordingly, understanding the factors behind the production of recombinant protein might lead to new avenues to increase the solubility and functionality of recombinant proteins. During the development of the present thesis we have used a wide range of techniques to analyse protein aggregation process in three different frameworks: in vitro, in vivo and in silico. The depositional properties of polypeptides differing in structure, sequence, and function were studied. The data obtained reveal the importance of the intrinsic polypeptide chain properties to protein aggregation and reveal the general rules controlling polypeptide deposition. This information permitted the development of an algorithm able to locate key depositional regions and calculate the global aggregation propensity of a protein starting from their amino acid sequence. This tool can be used for the analysis of the aggregation properties of large protein sets as show here for cytosolic bacterial proteins. <br/>Overall, the results collected in the present thesis could be valuable for biomedicine area suggesting new therapeutic targets to fight against depositional diseases as well as new approaches to increase the protein quality during protein production. It is also shown that folding and aggregation turn two be two side of the same coin that compete with each other.Universitat Autònoma de BarcelonaVendrell i Roca, JosepVentura i Zamora, SalvadorUniversitat Autònoma de Barcelona. Departament de Bioquímica i Biologia Molecular2011201020102010info:eu-repo/semantics/doctoralThesisinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfapplication/pdfhttp://www.tdx.cat/TDX-1222110-184311http://hdl.handle.net/10803/3625TDX (Tesis Doctorals en Xarxa)reponame:TDR. Tesis Doctorales en Redinstname:CBUC, CESCAInglésADVERTIMENT. L'accés als continguts d'aquesta tesi doctoral i la seva utilització ha de respectar els drets de la persona autora. Pot ser utilitzada per a consulta o estudi personal, així com en activitats o materials d'investigació i docència en els termes establerts a l'art. 32 del Text Refós de la Llei de Propietat Intel·lectual (RDL 1/1996). Per altres utilitzacions es requereix l'autorització prèvia i expressa de la persona autora. En qualsevol cas, en la utilització dels seus continguts caldrà indicar de forma clara el nom i cognoms de la persona autora i el títol de la tesi doctoral. No s'autoritza la seva reproducció o altres formes d'explotació efectuades amb finalitats de lucre ni la seva comunicació pública des d'un lloc aliè al servei TDX. Tampoc s'autoritza la presentació del seu contingut en una finestra o marc aliè a TDX (framing). Aquesta reserva de drets afecta tant als continguts de la tesi com als seus resums i índexs.info:eu-repo/semantics/openAccessoai:www.tdx.cat:10803/36252026-06-14T12:46:07Z
dc.title.none.fl_str_mv Sequential and structural determinants of protein aggregation
title Sequential and structural determinants of protein aggregation
spellingShingle Sequential and structural determinants of protein aggregation
Sánchez de Groot, Natalia
E.Coli
Agregació
Proteïna
Ciències Experimentals
57
577
title_short Sequential and structural determinants of protein aggregation
title_full Sequential and structural determinants of protein aggregation
title_fullStr Sequential and structural determinants of protein aggregation
title_full_unstemmed Sequential and structural determinants of protein aggregation
title_sort Sequential and structural determinants of protein aggregation
dc.creator.none.fl_str_mv Sánchez de Groot, Natalia
author Sánchez de Groot, Natalia
author_facet Sánchez de Groot, Natalia
author_role author
dc.contributor.none.fl_str_mv Vendrell i Roca, Josep
Ventura i Zamora, Salvador
Universitat Autònoma de Barcelona. Departament de Bioquímica i Biologia Molecular
dc.subject.none.fl_str_mv E.Coli
Agregació
Proteïna
Ciències Experimentals
57
577
topic E.Coli
Agregació
Proteïna
Ciències Experimentals
57
577
description The project entitled "Sequential and structural determinants of protein aggregation" aims to study the factors that control protein deposition but also tries to develop new strategies to facilitate its comprehension. <br/>Protein aggregation is related with an increasing number of human disorders such as Alzheimer's disease, Parkinson disease or type II diabetes. Understanding the determinants that modulate the deposition process is a necessary step to develop new strategies to tackle these debilitating pathologies. Additionally, the accumulation of heterologous protein as intracellular aggregates during recombinant expression represents one of the main problems in down stream processing. Accordingly, understanding the factors behind the production of recombinant protein might lead to new avenues to increase the solubility and functionality of recombinant proteins. During the development of the present thesis we have used a wide range of techniques to analyse protein aggregation process in three different frameworks: in vitro, in vivo and in silico. The depositional properties of polypeptides differing in structure, sequence, and function were studied. The data obtained reveal the importance of the intrinsic polypeptide chain properties to protein aggregation and reveal the general rules controlling polypeptide deposition. This information permitted the development of an algorithm able to locate key depositional regions and calculate the global aggregation propensity of a protein starting from their amino acid sequence. This tool can be used for the analysis of the aggregation properties of large protein sets as show here for cytosolic bacterial proteins. <br/>Overall, the results collected in the present thesis could be valuable for biomedicine area suggesting new therapeutic targets to fight against depositional diseases as well as new approaches to increase the protein quality during protein production. It is also shown that folding and aggregation turn two be two side of the same coin that compete with each other.
publishDate 2010
dc.date.none.fl_str_mv 2010
2010
2010
2011
dc.type.none.fl_str_mv info:eu-repo/semantics/doctoralThesis
info:eu-repo/semantics/publishedVersion
format doctoralThesis
status_str publishedVersion
dc.identifier.none.fl_str_mv http://www.tdx.cat/TDX-1222110-184311
http://hdl.handle.net/10803/3625
url http://www.tdx.cat/TDX-1222110-184311
http://hdl.handle.net/10803/3625
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Universitat Autònoma de Barcelona
publisher.none.fl_str_mv Universitat Autònoma de Barcelona
dc.source.none.fl_str_mv TDX (Tesis Doctorals en Xarxa)
reponame:TDR. Tesis Doctorales en Red
instname:CBUC, CESCA
instname_str CBUC, CESCA
reponame_str TDR. Tesis Doctorales en Red
collection TDR. Tesis Doctorales en Red
repository.name.fl_str_mv
repository.mail.fl_str_mv
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