TY - JOUR
T1 - Retinal proteins as model systems for membrane protein folding
AU - Tastan, Oznur
AU - Dutta, Arpana
AU - Booth, Paula
AU - Klein-Seetharaman, Judith
N1 - Funding Information:
We would like to thank Professor Charles Sanders of Vanderbilt University for asking his insightful question “Why can't rhodopsin be refolded?” at the Membrane Protein Folding Meeting of the Biophysical Society in Seoul, South Korea on May 19–22, 2013, inspiring the theme of this article. Thanks also to Fernanda Balem for the preparation of Fig. 2 . Research by the authors reviewed in this article has been funded in part by NSF CAREER grant CC044917 and NSF EAGER grant IIS-1144281 , National Institutes of Health Grant NLM108730 , a DAAD-Helmholtz Fellowship and a Royal Society Wolfson Merit Award , Leverhulme Research Fellowship as well as BBSRC grants ( BB/G002037/1 and BB/F013183/1 ) to PJB.
PY - 2014/5
Y1 - 2014/5
N2 - Experimental folding studies of membrane proteins are more challenging than water-soluble proteins because of the higher hydrophobicity content of membrane embedded sequences and the need to provide a hydrophobic milieu for the transmembrane regions. The first challenge is their denaturation: due to the thermodynamic instability of polar groups in the membrane, secondary structures in membrane proteins are more difficult to disrupt than in soluble proteins. The second challenge is to refold from the denatured states. Successful refolding of membrane proteins has almost always been from very subtly denatured states. Therefore, it can be useful to analyze membrane protein folding using computational methods, and we will provide results obtained with simulated unfolding of membrane protein structures using the Floppy Inclusions and Rigid Substructure Topography (FIRST) method. Computational methods have the advantage that they allow a direct comparison between diverse membrane proteins. We will review here both, experimental and FIRST studies of the retinal binding proteins bacteriorhodopsin and mammalian rhodopsin, and discuss the extension of the findings to deriving hypotheses on the mechanisms of folding of membrane proteins in general. This article is part of a Special Issue entitled: Retinal Proteins - You can teach an old dog new tricks.
AB - Experimental folding studies of membrane proteins are more challenging than water-soluble proteins because of the higher hydrophobicity content of membrane embedded sequences and the need to provide a hydrophobic milieu for the transmembrane regions. The first challenge is their denaturation: due to the thermodynamic instability of polar groups in the membrane, secondary structures in membrane proteins are more difficult to disrupt than in soluble proteins. The second challenge is to refold from the denatured states. Successful refolding of membrane proteins has almost always been from very subtly denatured states. Therefore, it can be useful to analyze membrane protein folding using computational methods, and we will provide results obtained with simulated unfolding of membrane protein structures using the Floppy Inclusions and Rigid Substructure Topography (FIRST) method. Computational methods have the advantage that they allow a direct comparison between diverse membrane proteins. We will review here both, experimental and FIRST studies of the retinal binding proteins bacteriorhodopsin and mammalian rhodopsin, and discuss the extension of the findings to deriving hypotheses on the mechanisms of folding of membrane proteins in general. This article is part of a Special Issue entitled: Retinal Proteins - You can teach an old dog new tricks.
KW - Bacteriorhodopsin
KW - Denatured states
KW - Membrane protein folding
KW - Rhodopsin
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U2 - 10.1016/j.bbabio.2013.11.021
DO - 10.1016/j.bbabio.2013.11.021
M3 - Review article
C2 - 24333783
AN - SCOPUS:84897112862
VL - 1837
SP - 656
EP - 663
JO - Biochimica et Biophysica Acta - Bioenergetics
JF - Biochimica et Biophysica Acta - Bioenergetics
SN - 0005-2728
IS - 5
ER -