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Arch Biochem Biophys. 2014 Dec 15;564:281-96. doi: 10.1016/j.abb.2014.07.017. Epub 2014 Jul 21.

Folding energetics and oligomerization of polytopic α-helical transmembrane proteins.

Author information

1
Department of Pharmacy and Biochemistry, Johannes Gutenberg-University Mainz, 55128 Mainz, Germany.
2
Interdisciplinary Nanoscience Center (iNANO), Department of Molecular Biology and Genetics, Center for Insoluble Protein Structures (inSPIN), Aarhus University, Gustav Wieds Vej 14, DK-8000 Aarhus C, Denmark.
3
Department of Pharmacy and Biochemistry, Johannes Gutenberg-University Mainz, 55128 Mainz, Germany. Electronic address: Dirk.Schneider@uni-mainz.de.

Abstract

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.

KEYWORDS:

Folding energetics; Membrane protein; Oligomerization; Protein folding

PMID:
25057769
DOI:
10.1016/j.abb.2014.07.017
[Indexed for MEDLINE]

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