3COC

Crystal Structure of D115A mutant of Bacteriorhodopsin

Summary for 3COC

• Entry DOI: 10.2210/pdb3coc/pdb
• Related: 1PY6 1XJI 3COC
• Descriptor: Bacteriorhodopsin, RETINAL (3 entities in total)
• Functional Keywords: membrane protein, membrane protein folding, hydrogen bond, chromophore, hydrogen ion transport, ion transport, photoreceptor protein, pyrrolidone carboxylic acid, receptor, retinal protein, sensory transduction, transmembrane, transport, proton transport
• Biological source: Halobacterium salinarum
• Cellular location: Cell membrane; Multi-pass membrane protein: P02945
• Total number of polymer chains: 2
• Total formula weight: 54339.85

Authors

Joh, N.H.,Faham, S.,Bowie, J.U. (deposition date: 2008-03-27, release date: 2008-04-08, Last modification date: 2024-10-30)

Primary citation

Joh, N.H.,Min, A.,Faham, S.,Whitelegge, J.P.,Yang, D.,Woods, V.L.,Bowie, J.U.
Modest stabilization by most hydrogen-bonded side-chain interactions in membrane proteins.
Nature, 453:1266-1270, 2008

PubMed Abstract: Understanding the energetics of molecular interactions is fundamental to all of the central quests of structural biology including structure prediction and design, mapping evolutionary pathways, learning how mutations cause disease, drug design, and relating structure to function. Hydrogen-bonding is widely regarded as an important force in a membrane environment because of the low dielectric constant of membranes and a lack of competition from water. Indeed, polar residue substitutions are the most common disease-causing mutations in membrane proteins. Because of limited structural information and technical challenges, however, there have been few quantitative tests of hydrogen-bond strength in the context of large membrane proteins. Here we show, by using a double-mutant cycle analysis, that the average contribution of eight interhelical side-chain hydrogen-bonding interactions throughout bacteriorhodopsin is only 0.6 kcal mol(-1). In agreement with these experiments, we find that 4% of polar atoms in the non-polar core regions of membrane proteins have no hydrogen-bond partner and the lengths of buried hydrogen bonds in soluble proteins and membrane protein transmembrane regions are statistically identical. Our results indicate that most hydrogen-bond interactions in membrane proteins are only modestly stabilizing. Weak hydrogen-bonding should be reflected in considerations of membrane protein folding, dynamics, design, evolution and function.

PubMed: 18500332
DOI: 10.1038/nature06977

Experimental method

X-RAY DIFFRACTION (2.31 Å)