Folding energetics and oligomerization of polytopic α-helical transmembrane proteins

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  • Jennifer Neumann, Department of Pharmacy and Biochemistry, Johannes Gutenberg-University Mainz, 55128 Mainz, Germany., Denmark
  • Noreen Klein, Department of Pharmacy and Biochemistry, Johannes Gutenberg-University Mainz, 55128 Mainz, Germany., Denmark
  • Daniel Otzen
  • Dirk Schneider, Department of Pharmacy and Biochemistry, Johannes Gutenberg-University Mainz, 55128 Mainz, Germany. Electronic address: Dirk.Schneider@uni-mainz.de.

While interactions of single-span transmembrane helices have been studied to a significant extent in the past years, the folding of polytopic α-helical transmembrane proteins as well as their oligomerization, are far less analyzed and understood. The goal of the few thus far performed thermodynamic studies, in which unfolding of polytopic TM proteins was described, was to achieve a mild, potentially reversible unfolding process, to finally derive thermodynamic parameters for the reverse folding pathway. In the first part of this review, we summarize the studies analyzing the thermodynamic stability and folding pathways of polytopic transmembrane proteins. Based on these studies, we deduce some common principles, guiding transmembrane protein unfolding and folding, important for the design of future folding/unfolding studies. Furthermore, the discussed observations can conceptually guide an experimental search for proper in vitro transmembrane protein refolding conditions. In many of the resolved membrane protein structures, individual monomers interact to form higher ordered oligomers. In most cases, oligomerization of those monomeric units appears to be intimately linked to the protein function, and folding of the individual protomers might even occur only after interaction. In the second part of this review, we discuss folding pathways of oligomeric α-helical transmembrane proteins as well as causes and consequences of α-helical transmembrane protein oligomerization.

Original languageEnglish
JournalArchives of Biochemistry and Biophysics
Volume564
Pages (from-to)281–296
Number of pages16
ISSN0003-9861
DOIs
Publication statusPublished - 15 Dec 2014

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