Conformationally controlled pK-switching in membrane proteins: One more mechanism specific to the enzyme catalysis?

AbstractInternal proton displacements in several membrane photosynthetic enzymes are analyzed in relation to general mechanisms of enzymatic catalysis. In the bacterial photosynthetic reaction center (RC) and in bacteriorhodopsin (BR), carboxy residues (Glu-212 in the RC L-subunit and Asp-96 in BR) serve as indispensable intrinsic proton donors. Both carboxyls are protonated prior to the proton-donation step, because their pK values are shifted to ≥12.0 by the interaction with the protein and/or substrate. In both cases, the proton transfer reactions are preceded by conformational changes that, supposedly, let water interact with the carboxyls. These changes switch over the pK values of the carboxyls to ≤6.0 and 7.1 in the RC and BR, respectively. The sharp increase in the proton-donating ability of the carboxyls drives the reaction cycles. This kind of catalytic mechanism, where a strong general acid or base emerges, when needed, as a result of a conformational change can be denoted as a conformationally controlled pK-switching. Generally, the ability of enzymes to go between isoenergetic conformations that differ widely in the reactivity of the catalytic group(s) may be of crucial importance to the understanding of enzymatic catalysis. Particularly, the pK-switching concept could help to reconcile the contradictory views on the functional protonation state of the redox-active tyrosine YZ in the oxygen-evolving photosystem II. It is conceivable that YZ switches its pK from ∼4.5 to ≥10.0 upon the last, rate-limiting step of water oxidation. By turning into a strong base, tyrosine assists then in abstracting a proton from the bound substrate water and helps to drive the dioxygen formation

On the origin of life in the Zinc world: 1. Photosynthesizing, porous edifices built of hydrothermally precipitated zinc sulfide as cradles of life on Earth

<p>Abstract</p> <p>Background</p> <p>The complexity of the problem of the origin of life has spawned a large number of possible evolutionary scenarios. Their number, however, can be dramatically reduced by the simultaneous consideration of various bioenergetic, physical, and geological constraints.</p> <p>Results</p> <p>This work puts forward an evolutionary scenario that satisfies the known constraints by proposing that life on Earth emerged, powered by UV-rich solar radiation, at photosynthetically active porous edifices made of precipitated zinc sulfide (ZnS) similar to those found around modern deep-sea hydrothermal vents. Under the high pressure of the primeval, carbon dioxide-dominated atmosphere ZnS could precipitate at the surface of the first continents, within reach of solar light. It is suggested that the ZnS surfaces (1) used the solar radiation to drive carbon dioxide reduction, yielding the building blocks for the first biopolymers, (2) served as templates for the synthesis of longer biopolymers from simpler building blocks, and (3) prevented the first biopolymers from photo-dissociation, by absorbing from them the excess radiation. In addition, the UV light may have favoured the selective enrichment of photostable, RNA-like polymers. Falsification tests of this hypothesis are described in the accompanying article (A.Y. Mulkidjanian, M.Y. Galperin, <it>Biology Direct </it>2009, 4:27).</p> <p>Conclusion</p> <p>The suggested "Zn world" scenario identifies the geological conditions under which photosynthesizing ZnS edifices of hydrothermal origin could emerge and persist on primordial Earth, includes a mechanism of the transient storage and utilization of solar light for the production of diverse organic compounds, and identifies the driving forces and selective factors that could have promoted the transition from the first simple, photostable polymers to more complex living organisms.</p> <p>Reviewers</p> <p>This paper was reviewed by Arcady Mushegian, Simon Silver (nominated by Arcady Mushegian), Antoine Danchin (nominated by Eugene Koonin) and Dieter Braun (nominated by Sergey Maslov).</p> <p indent="3">- ....<it>without parent by spontaneous birth</it></p> <p indent="3"><it>Rise the first specks of animated earth</it>.</p> <p indent="3">Erasmus Darwin, <it>Temple of Nature</it>, 1802 <abbrgrp><abbr bid="B1">1</abbr></abbrgrp></p

On the origin of life in the Zinc world. 2. Validation of the hypothesis on the photosynthesizing zinc sulfide edifices as cradles of life on Earth

<p>Abstract</p> <p>Background</p> <p>The accompanying article (A.Y. Mulkidjanian, <it>Biology Direct </it>4:26) puts forward a detailed hypothesis on the role of zinc sulfide (ZnS) in the origin of life on Earth. The hypothesis suggests that life emerged within compartmentalized, photosynthesizing ZnS formations of hydrothermal origin (the Zn world), assembled in sub-aerial settings on the surface of the primeval Earth.</p> <p>Results</p> <p>If life started within photosynthesizing ZnS compartments, it should have been able to evolve under the conditions of elevated levels of Zn²⁺ions, byproducts of the ZnS-mediated photosynthesis. Therefore, the Zn world hypothesis leads to a set of testable predictions regarding the specific roles of Zn²⁺ions in modern organisms, particularly in RNA and protein structures related to the procession of RNA and the "evolutionarily old" cellular functions. We checked these predictions using publicly available data and obtained evidence suggesting that the development of the primeval life forms up to the stage of the Last Universal Common Ancestor proceeded in zinc-rich settings. Testing of the hypothesis has revealed the possible supportive role of manganese sulfide in the primeval photosynthesis. In addition, we demonstrate the explanatory power of the Zn world concept by elucidating several points that so far remained without acceptable rationalization. In particular, this concept implies a new scenario for the separation of Bacteria and Archaea and the origin of Eukarya.</p> <p>Conclusion</p> <p>The ability of the Zn world hypothesis to generate non-trivial veritable predictions and explain previously obscure items gives credence to its key postulate that the development of the first life forms started within zinc-rich formations of hydrothermal origin and was driven by solar UV irradiation. This concept implies that the geochemical conditions conducive to the origin of life may have persisted only as long as the atmospheric CO₂pressure remained above ca. 10 bar. This work envisions the first Earth biotopes as photosynthesizing and habitable areas of porous ZnS and MnS precipitates around primeval hot springs. Further work will be needed to provide details on the life within these communities and to elucidate the primordial (bio)chemical reactions.</p> <p>Reviewers</p> <p>This article was reviewed by Arcady Mushegian, Eugene Koonin, and Patrick Forterre. For the full reviews, please go to the Reviewers' reports section.</p

Evolution of Cell Division: From Shear Mechanics to Complex Molecular Machineries

Cell division depends on sophisticated molecular machinery. However, wall-less forms of bacteria use a much simpler mechanism that mimics spontaneous division of synthetic lipid vesicles. Mercier et al. (2013) show that this “mechanical” division can be activated by increased lipid synthesis. Conceivably, the first cells divided via this route

Survival of the fittest before the beginning of life: selection of the first oligonucleotide-like polymers by UV light

BACKGROUND: A key event in the origin of life on this planet has been formation of self-replicating RNA-type molecules, which were complex enough to undergo a Darwinian-type evolution (origin of the "RNA world"). However, so far there has been no explanation of how the first RNA-like biopolymers could originate and survive on the primordial Earth. RESULTS: As condensation of sugar phosphates and nitrogenous bases is thermodynamically unfavorable, these compounds, if ever formed, should have undergone rapid hydrolysis. Thus, formation of oligonucleotide-like structures could have happened only if and when these structures had some selective advantage over simpler compounds. It is well known that nitrogenous bases are powerful quenchers of UV quanta and effectively protect the pentose-phosphate backbones of RNA and DNA from UV cleavage. To check if such a protection could play a role in abiogenic evolution on the primordial Earth (in the absence of the UV-protecting ozone layer), we simulated, by using Monte Carlo approach, the formation of the first oligonucleotides under continuous UV illumination. The simulations confirmed that UV irradiation could have worked as a selective factor leading to a relative enrichment of the system in longer sugar-phosphate polymers carrying nitrogenous bases as UV-protectors. Partial funneling of the UV energy into the condensation reactions could provide a further boost for the oligomerization. CONCLUSION: These results suggest that accumulation of the first polynucleotides could be explained by their abiogenic selection as the most UV-resistant biopolymers

The cytochrome bc1 complex of Rhodobacter capsulatus: ubiquinol oxidation in a dimeric Q-cycle?

AbstractWe studied the cytochrome bc1 complex (hereafter bc) by flash excitation of Rhodobacter capsulatus chromatophores. The reduction of the high-potential heme bh of cytochrome b (at 561 nm) and of cytochromes c (at 552 nm) and the electrochromic absorption transients (at 524 nm) were monitored after the first and second flashes of light, respectively. We kept the ubiquinone pool oxidized in the dark and concerned for the ubiquinol formation in the photosynthetic reaction center only after the second flash. Surprisingly, the first flash caused the oxidation of about one ubiquinol per bc dimer. Based on these and other data we propose a dimeric Q-cycle where the energetically unfavorable oxidation of the first ubiquinol molecule by one of the bc monomers is driven by the energetically favorable oxidation of the second ubiquinol by the other bc monomer resulting in a pairwise oxidation of ubiquinol molecules by the dimeric bc in the dark. The residual unpaired ubiquinol supposedly remains on the enzyme and is then oxidized after the first flash

Transient accumulation of elastic energy in proton translocating ATP synthase

AbstractATP synthase is conceived as a rotatory engine with two reversible drives, the proton-transporting membrane portion, F0, and the catalytic peripheral portion, F1. They are mounted on a central shaft (subunit γ) and held together by an eccentric bearing. It is established that the hydrolysis of three molecules of ATP in F1 drives the shaft over a full circle in three steps of 120° each. Proton flow through F0 probably generates a 12-stepped rotation of the shaft so that four proton-translocating steps of 30° each drive the synthesis of one molecule of ATP. We addressed the elasticity of the transmission between F0 and F1 in a model where the four smaller steps in F0 load a torsional spring which is only released under liberation of ATP from F1. The kinetic model of an elastic ATP synthase described a wealth of published data on the synthesis/hydrolysis of ATP by F0F1 and on proton conduction by F0 as function of the pH and the protonmotive force. The pK values of the proton-carrying group interacting with the acidic and basic sides of the membrane were estimated as 5.3–6.4 and 8.0–8.3, respectively

Evolutionary primacy of sodium bioenergetics

<p>Abstract</p> <p>Background</p> <p>The F- and V-type ATPases are rotary molecular machines that couple translocation of protons or sodium ions across the membrane to the synthesis or hydrolysis of ATP. Both the F-type (found in most bacteria and eukaryotic mitochondria and chloroplasts) and V-type (found in archaea, some bacteria, and eukaryotic vacuoles) ATPases can translocate either protons or sodium ions. The prevalent proton-dependent ATPases are generally viewed as the primary form of the enzyme whereas the sodium-translocating ATPases of some prokaryotes are usually construed as an exotic adaptation to survival in extreme environments.</p> <p>Results</p> <p>We combine structural and phylogenetic analyses to clarify the evolutionary relation between the proton- and sodium-translocating ATPases. A comparison of the structures of the membrane-embedded oligomeric proteolipid rings of sodium-dependent F- and V-ATPases reveals nearly identical sets of amino acids involved in sodium binding. We show that the sodium-dependent ATPases are scattered among proton-dependent ATPases in both the F- and the V-branches of the phylogenetic tree.</p> <p>Conclusion</p> <p>Barring convergent emergence of the same set of ligands in several lineages, these findings indicate that the use of sodium gradient for ATP synthesis is the ancestral modality of membrane bioenergetics. Thus, a primitive, sodium-impermeable but proton-permeable cell membrane that harboured a set of sodium-transporting enzymes appears to have been the evolutionary predecessor of the more structurally demanding proton-tight membranes. The use of proton as the coupling ion appears to be a later innovation that emerged on several independent occasions.</p> <p>Reviewers</p> <p>This article was reviewed by J. Peter Gogarten, Martijn A. Huynen, and Igor B. Zhulin. For the full reviews, please go to the Reviewers' comments section.</p