Department of Biochemistry and Cell Biology
Kevin R. MacKenzie
The two stage model of membrane protein folding suggests that the properties of a lipid environment may make the folding and stability of integral membrane proteins easier to understand than that of their soluble counterparts. For proteins that span the bilayer as a-helices, each transmembrane segment can be viewed as an independent folding domain: the net hydrophobicity of these segments precludes their dissociation from the membrane, while the cost of breaking hydrogen bonds within a low dielectric medium prevents the helices from unfolding.
If each transmembrane domain were to form a canonical helix, the specificity of helix-helix interactions would depend exclusively on the contacts made between sidechains presented by these helices. A description of the physical basis for these sidechain interactions might therefore be sufficient to predict membrane protein structure and stability from primary sequence.
Computational, biophysical, biochemical, molecular biological, and genetic studies have all provided insight into the forces and factors governing the stability and folding of membrane proteins. The selection of references presented below gives a few examples of the diverse approaches that have been brought to this subject, as well as some of the interesting findings that have resulted. The reviews at the bottom of the list will provide a more complete and balanced overview of the state of the membrane protein folding literature.
JL Popot and DM Engelman Biochemistry (1990) 29(17), 4031-7
The two-stage model provides a conceptual framework for thinking about the thermodynamics of helix-helix association in bilayers.
in a biological membrane"
WP Russ and DM Engelman PNAS (1999) 96, 863-868
An assay for the self-association of single transmembrane domains in E. coli membranes based on reporter gene expression that can be quantitated or used in a selection scheme.
WP Russ and DM Engelman J.Mol.Biol. (2000), 296(3), 911-9
Identification of sequence patterns in strongly oligomerizing transmembrane domains selected from a random library.
XN Zhang, J Zhu and JL Spudich PNAS (1999) 96(3), 857-62
KH Jung and JL Spudich J Bacteriol (1998) 180(8), 2033-42
Genetic analysis and reverse genetics experiments identify interactions between transmembrane helices of a photosensitive seven transmembrane domain receptor and a two transmembrane domain transducer protein involved in archaeal phototaxis.
proteins at membrane interfaces"
WC Wimley and SH White Nat Struct Biol (1996) 3(10), 842-8
peptide model system: implications for protein stability"
WC Wimley, K Gawrisch, TP Creamer and SH White PNAS (1996) 93(7), 2985-90
SC Li and CM Deber Nat Struct Biol (1994) 1(6), 368-73
The study of peptides and peptide models has yielded useful insights into the physicochemical principles of MP folding and stability (despite the paucity of structural and energetic information about intact MPs).
JU Bowie J Mol Biol (1997) 272(5), 780-9
SH White and WC Wimley Annu Rev Biophys Biomol Struct (1999) 28, 319-65
T Haltia and E Freire Biochim Biophys Acta (1995) 1228(1), 1-27
(corrected)
T Haltia and E Freire Biochim Biophys Acta (1995) 1241(2), 295-322
F Dumas, MC Lebrun and JF Tocanne FEBS Lett (1999) 458(3), 271-7
SH White and WC Wimley Biochim Biophys Acta (1998) 1376(3), 339-52
LP Liu and CM Deber Biopolymers (1998) 47(1), 41-62
I Mingarro, G von Heijne and P Whitley Trends Biotechnol (1997) 15(10), 432-7
PJ Booth and AR Curran Curr Opin Struct Biol (1999) 9(1), 115-21
M van Geest and JS Lolkema Microbiol Mol Biol Rev (2000) 64(1), 13-33
AJ Driessen and P Fekkes Microbiol Mol Biol Rev (1999) 63(1), 161-73
PN Danese and TJ Silhavy Annu Rev Genet (1998) 32, 59-94
SA Teter and DJ Klionsky Trends Cell Biol (1999) 9(11), 428-31
H Sakai and T Tsukihara J Biochem (Tokyo) (1998) 124(6), 1051-9
FM Marassi and SJ Opella Curr Opin Struct Biol (1998) 8(5), 640-8
S Frillingos, M Sathin-Toth, J Wu and HR Kaback FASEB J (1998) 12(13), 1281-99