Side-chain contributions to membrane protein structure and stability.


Abstract

The molecular forces that stabilize membrane protein structure are poorly understood. To investigate these forces we introduced alanine substitutions at 24 positions in the B helix of bacteriorhodopsin and examined their effects on structure and stability. Although most of the results can be rationalized in terms of the folded structure, there are a number of surprises. (1) We find a remarkably high frequency of stabilizing mutations (17%), indicating that membrane proteins are not highly optimized for stability. (2) Helix B is kinked, with the kink centered around Pro50. The P50A mutation has no effect on stability, however, and a crystal structure reveals that the helix remains bent, indicating that tertiary contacts dominate in the distortion of this helix. (3) We find that the protein is stabilized by about 1kcal/mol for every 38A(2) of surface area buried, which is quite similar to soluble proteins in spite of their dramatically different environments. (4) We find little energetic difference, on average, in the burial of apolar surface or polar surface area, implying that van der Waals packing is the dominant force that drives membrane protein folding. Study holds ProTherm entries: 17314, 17315, 17316, 17317, 17318, 17319, 17320, 17321, 17322, 17323, 17324, 17325, 17326, 17327, 17328, 17329, 17330, 17331, 17332, 17333, 17334, 17335, 17336, 17337 Extra Details: 15 mM DMPC and 16 mM CHAPSO were added in the experiment. bacteriorhodopsin; hydrogen bond; van der Waals; protein folding; helix kink

Submission Details

ID: SfZyHtsR3

Submitter: Connie Wang

Submission Date: April 24, 2018, 8:49 p.m.

Version: 1

Publication Details
Faham S;Yang D;Bare E;Yohannan S;Whitelegge JP;Bowie JU,J. Mol. Biol. (2004) Side-chain contributions to membrane protein structure and stability. PMID:14659758
Additional Information

Structure view and single mutant data analysis

Study data

No weblogo for data of varying length.
Colors: D E R H K S T N Q A V I L M F Y W C G P
 

Data Distribution

Studies with similar sequences (approximate matches)

Correlation with other assays (exact sequence matches)


Relevant PDB Entries

Structure ID Release Date Resolution Structure Title
1AP9 1997-07-26T00:00:00+0000 2.35 X-RAY STRUCTURE OF BACTERIORHODOPSIN FROM MICROCRYSTALS GROWN IN LIPIDIC CUBIC PHASES
1AT9 1997-08-20T00:00:00+0000 3.0 STRUCTURE OF BACTERIORHODOPSIN AT 3.0 ANGSTROM DETERMINED BY ELECTRON CRYSTALLOGRAPHY
1BCT 1993-07-07T00:00:00+0000 0 THREE-DIMENSIONAL STRUCTURE OF PROTEOLYTIC FRAGMENT 163-231 OF BACTERIOOPSIN DETERMINED FROM NUCLEAR MAGNETIC RESONANCE DATA IN SOLUTION
1BHA 1993-10-11T00:00:00+0000 0 THREE-DIMENSIONAL STRUCTURE OF (1-71) BACTERIOOPSIN SOLUBILIZED IN METHANOL-CHLOROFORM AND SDS MICELLES DETERMINED BY 15N-1H HETERONUCLEAR NMR SPECTROSCOPY
1BHB 1993-10-11T00:00:00+0000 0 Three-dimensional structure of (1-71) bacterioopsin solubilized in methanol-chloroform and SDS micelles determined by 15N-1H heteronuclear NMR spectroscopy
1BM1 1998-07-28T00:00:00+0000 3.5 CRYSTAL STRUCTURE OF BACTERIORHODOPSIN IN THE LIGHT-ADAPTED STATE
1BRD 1990-05-23T00:00:00+0000 3.5 Model for the structure of Bacteriorhodopsin based on high-resolution Electron Cryo-microscopy
1BRR 1998-07-28T00:00:00+0000 2.9 X-RAY STRUCTURE OF THE BACTERIORHODOPSIN TRIMER/LIPID COMPLEX
1BRX 1998-05-28T00:00:00+0000 2.3 BACTERIORHODOPSIN/LIPID COMPLEX
1C3W 1999-07-28T00:00:00+0000 1.55 BACTERIORHODOPSIN/LIPID COMPLEX AT 1.55 A RESOLUTION

Relevant UniProtKB Entries

Percent Identity Matching Chains Protein Accession Entry Name
100.0 Bacteriorhodopsin P02945 BACR_HALSA