Potential Proton-Release Channels in Bacteriorhodopsin

• Published in: Chemphyschem 2008-12, Vol.9 (18), p.2751-2758
• Main Authors: Chaumont, Alain, Baer, Marcel, Mathias, Gerald, Marx, Dominik
• Format: Article
• Language: English
• Subjects: Amino Acids; Bacteria; bacteriorhodopsin; Bacteriorhodopsins - chemistry; Chemical Sciences; Computer Simulation; Hydrogen Bonding; Models, Molecular; molecular dynamics; Protein Conformation; proteins; Proton Pumps - chemistry; Proton Pumps - metabolism; proton transfer; Protons; Water
• ISSN: 1439-4235; 1439-7641
• DOI: 10.1002/cphc.200800471

The protein bacteriorhodopsin pumps protons across a bacterial membrane; its pumping cycle is triggered by the photoisomerization of a retinal cofactor and involves multiple proton‐transfer reactions between intermittent protonation sites. These transfers are either direct or mediated by hydrogen‐bonded networks, which may include internal water molecules. The terminal step of the proton‐transfer sequence is the proton release from a pocket near Glu194 and Glu204 to the extracellular bulk during the transition from the L to the M photointermediate states. The polar and charged side chains connecting these two regions in the crystal structures show no structural changes between the initial bR state and the L/M states, and no intermittent protonation changes have been detected so far in this region. Based on biomolecular simulations, we propose two potential proton‐release channels, which connect the release pocket to the extracellular medium. In simulations of the L photointermediate we observe bulk water entering these channels and forming transient hydrogen‐bonded networks, which could serve as fast deprotonation pathways from the release pocket to the bulk via a Grotthuss mechanism. For the first channel, we find that the triple Arg7, Glu9, and Tyr79 acts as a valve, thereby gating water uptake and release. The second channel has two release paths, which split at the position Asn76/Pro77 underneath the release group. Here, water molecules either exchange directly with the bulk or diffuse within the protein towards Arg 134/Lys129, where the exchange with the bulk occurs. Bacteriorhodopsin pumps protons across bacterial membranes via multiple proton‐transfer reactions, which can take place either directly or through hydrogen‐bonded networks involving internal water molecules. The terminal step of the transfer process is a proton release from a pocket near Glu194 and Glu204 to the extracellular medium. Two possible release channels are proposed based on biomolecular simulations (see figure).