The in Vivo and in Vitro Aggregation Properties of Globular Proteins Correlate With Their Conformational Stability: The SH3 Case

Alba Espargaró, Virginia Castillo, Natalia S. de Groot, Salvador Ventura

Research output: Contribution to journalArticleResearchpeer-review

49 Citations (Scopus)

Abstract

Protein misfolding and deposition underlie an increasing number of debilitating human disorders and constitute a problem of major concern in biotechnology. In the last years, in vitro studies have provided valuable insights into the physicochemical principles underlying protein aggregation. Nevertheless, information about the determinants of protein deposition within the cell is scarce and only a few systematic studies comparing in vitro and in vivo data have been reported. Here, we have used the SH3 domain of α-spectrin as a model globular protein in an attempt to understand the relationship between protein aggregation in the test-tube and in the more complex cellular environment. The investigation of the aggregation in Escherichia coli of this domain and a large set of mutants, together with the analysis of their sequential and conformational properties allowed us to evaluate the contribution of different polypeptidic factors to the cellular deposition of globular proteins. The data presented here suggest that the rules that govern in vitro protein aggregation are also valid in in vivo contexts. They also provide relevant insights into intracellular protein deposition in both conformational diseases and recombinant protein production. © 2008 Elsevier Ltd. All rights reserved.
Original languageEnglish
Pages (from-to)1116-1131
JournalJournal of Molecular Biology
Volume378
DOIs
Publication statusPublished - 16 May 2008

Keywords

  • SH3 domains
  • protein aggregation
  • protein folding
  • protein production
  • protein stability

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