Oxygen content of transmembrane proteins over macroevolutionary time scalesAcquisti, Claudia; Kleffe, Jürgen; Collins, Sinéad
doi: 10.1038/nature05450pmid: 17183269
We observe that the time of appearance of cellular compartmentalization correlates with atmospheric oxygen concentration. To explore this correlation, we predict and characterize the topology of all transmembrane proteins in 19 taxa and correlate differences in topology with historical atmospheric oxygen concentrations. Here we show that transmembrane proteins, individually and as a group, were probably selectively excluding oxygen in ancient ancestral taxa, and that this constraint decreased over time when atmospheric oxygen levels rose. As this constraint decreased, the size and number of communication-related transmembrane proteins increased. We suggest the hypothesis that atmospheric oxygen concentrations affected the timing of the evolution of cellular compartmentalization by constraining the size of domains necessary for communication across membranes.
Crystal structure of a protein phosphatase 2A heterotrimeric holoenzymeCho, Uhn Soo; Xu, Wenqing
doi: 10.1038/nature05351pmid: 17086192
Protein phosphatase 2A (PP2A) is a principal Ser/Thr phosphatase, the deregulation of which is associated with multiple human cancers, Alzheimer’s disease and increased susceptibility to pathogen infections. How PP2A is structurally organized and functionally regulated remains unclear. Here we report the crystal structure of an AB′C heterotrimeric PP2A holoenzyme. The structure reveals that the HEAT repeats of the scaffold A subunit form a horseshoe-shaped fold, holding the catalytic C and regulatory B′ subunits together on the same side. The regulatory B′ subunit forms pseudo-HEAT repeats and interacts with the C subunit near the active site, thereby defining substrate specificity. The methylated carboxy-terminal tail of the C subunit interacts with a highly negatively charged region at the interface between A and B′ subunits, suggesting that the C-terminal carboxyl methylation of the C subunit promotes B′ subunit recruitment by neutralizing charge repulsion. Together, our structural results establish a crucial foundation for understanding PP2A assembly, substrate recruitment and regulation.
High-level similarity of dentitions in carnivorans and rodentsEvans, Alistair R.; Wilson, Gregory P.; Fortelius, Mikael; Jernvall, Jukka
doi: 10.1038/nature05433pmid: 17167416
Palaeontologists can reconstruct the diets of extinct animals as a pointer to their lifestyles by painstaking comparison of fossil teeth with those of comparable living animals . A new method, based on a 'virtual' teeth database compiled from 441 digital images of teeth from 81 carnivore and rodent species, is less time consuming and may be more accurate. In the example of the carnivores and rodents, the dental comparisons show that the surface complexity of tooth crowns directly reflects the food that is eaten. The sheer variety of different diets adopted by living species means that the new method is particularly useful for fossils with no close analogues among living species.
A prokaryotic proton-gated ion channel from the nicotinic acetylcholine receptor familyBocquet, Nicolas; Prado de Carvalho, Lia; Cartaud, Jean; Neyton, Jacques; Le Poupon, Chantal; Taly, Antoine; Grutter, Thomas; Changeux, Jean-Pierre; Corringer, Pierre-Jean
doi: 10.1038/nature05371pmid: 17167423
Ligand-gated ion channels (LGICs) mediate excitatory and inhibitory transmission in the nervous system. Among them, the pentameric or ‘Cys-loop’ receptors (pLGICs) compose a family that until recently was found in only eukaryotes. Yet a recent genome search identified putative homologues of these proteins in several bacterial species
1
. Here we report the cloning, expression and functional identification of one of these putative homologues from the cyanobacterium Gloeobacter violaceus. It was expressed as a homo-oligomer in HEK 293 cells and Xenopus oocytes, generating a transmembrane cationic channel that is opened by extracellular protons and shows slow kinetics of activation, no desensitization and a single channel conductance of 8 pS. Electron microscopy and cross-linking experiments of the protein fused to the maltose-binding protein and expressed in Escherichia coli are consistent with a homo-pentameric organization. Sequence comparison shows that it possesses a compact structure, with the absence of the amino-terminal helix, the canonical disulphide bridge and the large cytoplasmic domain found in eukaryotic pLGICs. Therefore it embodies a minimal structure required for signal transduction. These data establish the prokaryotic origin of the family. Because Gloeobacter violaceus carries out photosynthesis and proton transport at the cytoplasmic membrane
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, this new proton-gated ion channel might contribute to adaptation to pH change.