Articles in 2007

The crystal structure of the maltose transporter, in complex with its periplasmic maltose-binding protein, at 2.8 Å resolution is presented. Because both ATP and maltose are bound and a mutation that prevents ATP hydrolysis has been introduced, the complex has been captured in an intermediate state and a mechanism for maltose transport proposed.

The presence of conformational substates of a catalytically competent 'closed' state in the ligand-free form of adenylate kinase is detected. Molecular dynamics simulations indicated that the partially closed conformations were sampled in nanoseconds, and NMR and single-molecule FRET experiments revealed the sampling of a fully closed conformation occurring on the microsecond-to-millisecond timescale.

One of two papers that demonstrates the importance of the lipid-exposed 'paddle' motif in voltage-dependant ion channels by showing that paddle function can be faithfully conserved when transplanted into distantly-related channels. The work also underscores the mobility of this motif within the membrane.

The second of two papers about the mechanism of voltage-activation of ion channels describes a high resolution structure of a modified Kv1.2 potassium channel surrounded by a bilayer-like arrangement of lipids. The work reveals how critical positive charges in the paddle are stabilized by both lipid and protein interactions and suggests a way in which the paddle may move in response to voltage to open the channel pore.

The reprogramming of rhesus macaque adult fibroblasts into embryonic stem cells using somatic cell nuclear transfer is demonstrated. Until now, creating embryonic stem cells in this way has only been successful in mice. This success with primates suggests that this approach could work for generating patient-derived embryonic stem cells, which could be used to treat a variety of diseases without immune rejection.

An international consortium reports the genomic sequence for ten Drosophila species, and compares them to two other previously published Drosophila species. These data are invaluable for drawing evolutionary conclusions across an entire phylogeny of species at once.

The genomic sequences of 12 Drosophila species for conserved elements and describe the relationship between conservation and function for many specific sequence motifs.

Neutral theory, in which species do not interact, has been used to try to understand the relative species abundance of tropical forests, although its validity been questioned. A non-interacting theory with similarities and differences to conventional neutral theory is developed. The approach provides a unified and quantitatively accurate description of relative species abundance data from both tropical forests and coral reefs.

Acoustic information is detected by inner hair cells in mammalian cochlea and is transmitted to the brain via the auditory nerve. But auditory nerve activity is evident before the cochlear machinery develops the ability to process information. The mechanism that underlies this effect has been uncovered in a series of experiments, showing that supporting cells located in Kölliker's organ spontaneously release ATP, activating inner hair cells and thus auditory nerve fibres.

A combination of genetics and calcium imaging is used to detail the neuronal circuitry in Caenorhabditis elegans that allows odour-sensing neurons to activate or inhibit downstream interneurons controlling crawling and turning behaviours. The nerve cell connectivity and molecules used by this nematode to process olfactory information shows striking homologies with those used to sense light in mammalian retina

A combination of genetic tricks and fancy fluorescent proteins is used to develop the Technicolor version of Golgi staining, 'Brainbow', in which hundreds of individual neurons are painted, each with a distinctive hue. This technology should not only boost mapping efforts in normal or diseased brains, but could also be applied to other complex cell populations, such as the immune system.

Human CtIP (a homologue of yeast Sae2) interacts with the putative resection nuclease, the Mre11 complex, and enhances its nuclease activity. CtIP and Mre11 are both required for efficient homologous recombination, for recruitment of the ATR checkpoint kinase and single-strand binding protein RPA to the break, and for ATR activation. This shows how end resection, activation of the checkpoint, and repair are interrelated.

A computational model that spans molecular and cellular levels describing diffusion and PIN-facilitated auxin transport in and across cells within the root system is experimentally tested. The model strongly supports that plant roots are able to generate an auxin maximum and a highly robust auxin gradient with morphogenic properties.

The morphogen Hedgehog (HH) governs cell differentiation and proliferation in a diverse array of patterning events in many species. The seven-transmembrane protein Smoothened (SMO) transduces the HH signal across the plasma membrane, but molecular mechanisms of SMO activation are poorly understood. The mechanism by which the cytoplasmic tail of SMO transmits the HH signal across the plasma membrane is demonstrated.

Legionella pneumophila directs maturation of its intracellular host compartment through effector secretion through the type 4 secretion system Dot/Icm. In addition to its GEF activity, L. pneumophila DrrA is shown to possess GDF for Rab1 GTPase, an acitivty which has until now only been described for one eukaryotic protein.

High resolution structural information for G protein-coupled receptors has so far been limited to rhodopsin; here a crystal structure of the β₂AR adrenaline receptor is presented.

Integrins are cell adhesion receptors involved in a variety of signalling processes and are targeted by a number of bacterial and viral pathogens for adhesion or invasion. The gastric pathogen Helicobacter pylori's pilus protein CagL interacts with integrin, which subsequently triggers translocation and phoshorylation of the bacterial effector CagA.

A consortium reports the tripling of the number of genetic markers in Phase II of the International HapMap Project. This map of human genetic variation will continue to revolutionize discovery of susceptibility loci in common genetic diseases, and study of genes under selection in humans.