Sequential and structural determinants of protein aggregation

dc.contributor
Universitat Autònoma de Barcelona. Departament de Bioquímica i Biologia Molecular
dc.contributor.author
Sánchez de Groot, Natalia
dc.date.accessioned
2011-04-12T14:19:45Z
dc.date.available
2010-12-22
dc.date.issued
2010-01-26
dc.date.submitted
2010-12-22
dc.identifier.isbn
9788469320532
dc.identifier.uri
http://www.tdx.cat/TDX-1222110-184311
dc.identifier.uri
http://hdl.handle.net/10803/3625
dc.description.abstract
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.
cat
dc.format.mimetype
application/pdf
dc.language.iso
eng
dc.publisher
Universitat Autònoma de Barcelona
dc.rights.license
ADVERTIMENT. 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.
dc.source
TDX (Tesis Doctorals en Xarxa)
dc.subject
E.Coli
dc.subject
Agregació
dc.subject
Proteïna
dc.subject.other
Ciències Experimentals
dc.title
Sequential and structural determinants of protein aggregation
dc.type
info:eu-repo/semantics/doctoralThesis
dc.type
info:eu-repo/semantics/publishedVersion
dc.subject.udc
57
cat
dc.subject.udc
577
cat
dc.contributor.authoremail
natalia.sanchez@uab.es
dc.contributor.director
Vendrell i Roca, Josep
dc.contributor.director
Ventura i Zamora, Salvador
dc.rights.accessLevel
info:eu-repo/semantics/openAccess
dc.identifier.dl
B-34764-2010


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