Structure of an atypical FeoB G-domain reveals a putative domain-swapped dimer.

FeoB is a transmembrane protein involved in ferrous iron uptake in prokaryotic organisms. FeoB comprises a cytoplasmic soluble domain termed NFeoB and a C-terminal polytopic transmembrane domain. Recent structures of NFeoB have revealed two structural subdomains: a canonical GTPase domain and a five-helix helical domain. The GTPase domain hydrolyses GTP to GDP through a well characterized mechanism, a process which is required for Fe(2+) transport. In contrast, the precise role of the helical domain has not yet been fully determined. Here, the structure of the cytoplasmic domain of FeoB from Gallionella capsiferriformans is reported. Unlike recent structures of NFeoB, the G. capsiferriformans NFeoB structure is highly unusual in that it does not contain a helical domain. The crystal structures of both apo and GDP-bound protein forms a domain-swapped dimer

Human observations of late Quaternary coastal change: examples from Australia, Europe and the Pacific Islands

In the aftermath of the last ice age, when sea level rose along most of the world's coastline, the activities of coastal peoples were impacted by coastal submergence, land loss and sometimes isolation as offshore islands formed. In some parts of the world, there is clear evidence that people encoded their observations of postglacial sea-level rise into oral traditions that were communicated across hundreds of generations to reach us today in an intelligible form. In other contexts, people's observations of rising sea level are likely to have formed the foundations of ‘legends’ about undersea places and the peoples inhabiting them. For a selection of coastal sites in Australia and northwest Europe, this study discusses a range of contrasting situations in which culturally-grounded stories about coastal submergence, land loss and isolation plausibly recollect the nature and effects of postglacial sea-level rise. Using science-based histories of postglacial sea-level change, minimum ages are determined for each group of site-specific stories; in the case of Australia, these range from 7000–11,500 BP, for northwest Europe from 5500 to 9500 BP. For selected sites in the Pacific Islands, where human settlement about 3000 years BP post-dated the end of postglacial sea-level rise, localized submergence is recalled in traditional stories of local people. It is argued that studies of late Quaternary coastal evolution can often be filled out by adding details from stories preserved in local cultures, something which leads to a clearer picture of the human-societal impacts of coastal submergence and land loss than can be obtained from palaeoenvironmental reconstructions and geological evidence alone

Animal models for COVID-19

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the aetiological agent of coronavirus disease 2019 (COVID-19), an emerging respiratory infection caused by the introduction of a novel coronavirus into humans late in 2019 (frst detected in Hubei province, China). As of 18 September 2020, SARS-CoV-2 has spread to 215 countries, has infected more than 30 million people and has caused more than 950,000 deaths. As humans do not have pre-existing immunity to SARS-CoV-2, there is an urgent need to develop therapeutic agents and vaccines to mitigate the current pandemic and to prevent the re-emergence of COVID-19. In February 2020, the World Health Organization (WHO) assembled an international panel to develop animal models for COVID-19 to accelerate the testing of vaccines and therapeutic agents. Here we summarize the fndings to date and provides relevant information for preclinical testing of vaccine candidates and therapeutic agents for COVID-19.info:eu-repo/semantics/acceptedVersio

Factors determining intrinsic GDP release in GTPases: a structural and functional study of the ferrous iron transporter FeoB

Factors determining intrinsic GDP release in GTPases: A structural and functional study of the ferrous iron transporter FeoB FeoB is a prokaryotic membrane protein involved in ferrous iron transport. It comprises a membrane transporter domain tethered to a soluble N-terminal domain (NFeoB) comprising two subdomains: a GTPase domain and a helical domain. The mechanism linking iron uptake to GTPase activity remains unknown. Early functional characterisation of the GTPase domain demonstrated a slow intrinsic GTP hydrolysis rate and a weak GDP affinity. Given this combination, the GTPase domain would be almost constitutively bound to GTP. This is physiologically unlikely given that FeoB would then be constitutively ‘on’ if functioning as a channel, or have too slow a hydrolysis rate if the iron transport mechanism was powered by GTP hydrolysis. In an attempt to rationalise this conundrum, the crystal structure of the Escherichia coli (E. coli) NFeoB domain was determined. However, the structure alone provided limited insight into the biochemical rationale for the weak GDP affinity and slow GTP hydrolysis. The main focus of my thesis work was thus to understand the slow GTP hydrolysis and to investigate if this reflects the in vivo rate, and to provide a molecular understanding of the weak GDP affinity in NFeoB. In this work, it was demonstrated that the intrinsically slow GTP hydrolysis rate of FeoB could be accelerated by potassium. Comparison of nucleotide free and bound E. coli NFeoB structures revealed a large conformational change in the nucleotide binding G5 motif. The importance of sequence to this region was highlighted through alanine scanning mutational analysis. In particular, mutations at positions 2 and 3 of the G5 loop had a significant impact on nucleotide affinity, and also underwent the largest conformational changes in the comparison of the nucleotide free and GTP bound structures. To determine the order of events in GDP release, a chimeric NFeoB protein combining sequence and structural characteristics of both fast and slow GDP releasing GTPases was constructed. Biochemical analysis revealed uncoupled nucleotide affinity and release rates supporting a model whereby G5 loop movement promotes nucleotide release

LSM Proteins: Piecing together a Molecular Assembly

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Proteins from the Mobile Metagenome: Developments for High-Throughput Production

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I ‘Masque’ nuziali di Thomas Campion: tra rituali galanti e kermesse

Sul contributo interdisciplinare dato da Thomas Campion, poeta, compositore e autore di Masque, all'evoluzione in ambito giacomiano di quest'ultimo genere di spettacolo teatrale

Structural Characterisation of Membrane-Attached Protein Domains within Vibrio Integron/Cassette Arrays

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Structure to Function: Cassette-encoded proteins from deep sea hydrothermal vent bacteria

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