Structural and functional analysis of a phospho-dependent molecular switch: Rv1827 from Mycobacterium tuberculosis.

Forkhead-associated (FHA) domains have gained considerable prominence as ubiquitous phosphothreonine-dependent binding modules; however, their precise roles in Ser/Thr kinase pathways and mechanisms of regulation remain unclear. From experiments with Rv1827, an FHA domain–containing protein from Mycobacterium tuberculosis, a complete molecular description of an FHA-mediated Ser/Thr protein kinase signalling process is derived. First, binding of the FHA domain to each of three metabolic enzyme complexes regulates their catalytic activities but does not require priming phosphorylation. However, phosphorylation of a threonine residue within a conserved N-terminal motif of Rv1827 triggers its intramolecular association with the FHA domain of Rv1827, thus blocking its interactions with each of the three enzymes. The nuclear magnetic resonance structure of this inactivated form and further mutagenic studies show how a novel intramolecular phospho-switch blocks the access of the target enzymes to a common FHA interaction surface and how this shared surface accommodates three functionally related, but structurally diverse, binding partners. Thus a remarkable and unsuspected versatility in the FHA domain that allows for the transformation of multiple kinase inputs into various downstream regulatory signals has been revealed.

Climatic records over the past 30 ka from temperate Australia - a synthesis from the Oz-INTIMATE workgroup

Temperate Australia sits between the heat engine of the tropics and the cold Southern Ocean, encompassing a range of rainfall regimes and falling under the influence of different climatic drivers. Despite this heterogeneity, broad-scale trends in climatic and environmental change are evident over the past 30ka. During the early glacial period (~30-22ka) and the Last Glacial Maximum (~22-18ka), climate was relatively cool across the entire temperate zone and there was an expansion of grasslands and increased fluvial activity in regionally important Murray-Darling Basin. The temperate region at this time appears to be dominated by expanded sea ice in the Southern Ocean forcing a northerly shift in the position of the oceanic fronts and a concomitant influx of cold water along the southeast (including Tasmania) and southwest Australian coasts. The deglacial period (~18-12ka) was characterised by glacial recession and eventual disappearance resulting from an increase in temperature deduced from terrestrial records, while there is some evidence for climatic reversals (e.g. the Antarctic Cold Reversal) in high resolution marine sediment cores through this period. The high spatial density of Holocene terrestrial records reveals an overall expansion of sclerophyll woodland and rainforest taxa across the temperate region after ~12ka, presumably in response to increasing temperature, while hydrological records reveal spatially heterogeneous hydro-climatic trends. Patterns after ~6ka suggest higher frequency climatic variability that possibly reflects the onset of large scale climate variability caused by the El Niño/Southern Oscillation