X-ray diffraction reveals the intrinsic difference in the physical properties of membrane and soluble proteins.

Membrane proteins are distinguished from soluble proteins by their insertion into biological membranes. This insertion is achieved via a noticeable arrangement of hydrophobic amino acids that are exposed at the surface of the protein, and renders the interaction with the aliphatic tails of lipids more energetically favorable. This important difference between these two categories of proteins is the source of the need for a specific handling of membrane proteins, which transpired in the creation of new tools for their recombinant expression, purification and even crystallization. Following this line, we show here that crystals of membrane proteins display systematically higher diffraction anisotropy than those of soluble proteins. This phenomenon dramatically hampers structure solution and refinement, and has a strong impact on the quality of electron-density maps. A farther search for origins of this phenomenon showed that the type of crystallization, and thus the crystal packing, has no impact on anisotropy, nor does the nature or function of the membrane protein. Membrane proteins fully embedded within the membrane display equal anisotropy compared to the ones with extra membranous domains or fusions with soluble proteins. Overall, these results overturn common beliefs and call for a specific handling of their diffraction data

Au courant computation of the PDB to audit diffraction anisotropy of soluble and membrane proteins.

This data article makes available the informed computation of the whole Protein Data Bank (PDB) to investigate diffraction anisotropy on a large scale and to perform statistics. This data has been investigated in detail in "X-ray diffraction reveals the intrinsic difference in the physical properties of membrane and soluble proteins" [1]. Diffraction anisotropy is traditionally associated with absence of contacts in-between macromolecules within the crystals in a given direction of space. There are however many case that do not follow this empirical rule. To investigate and sort out this discrepancy, we computed diffraction anisotropy for every entry of the PDB, and put them in context of relevant metrics to compare X-ray diffraction in reciprocal space to the crystal packing in real space. These metrics were either extracted from PDB files when available (resolution, space groups, cell parameters, solvent content), or calculated using standard procedures (anisotropy, crystal contacts, presence of ligands). More specifically, we separated entries to compare soluble vs membrane proteins, and further separated the later in subcategories according to their insertion in the membrane, function, or type of crystallization (Type I vs Type II crystal packing). This informed database is being made available to investigators in the raw and curated formats that can be re-used for further downstream studies. This dataset is useful to test ideas and to ascertain hypothesis based on statistical analysis

A Common Ca2+-Driven Interdomain Module Governs Eukaryotic NCX Regulation

Na+/Ca2+ exchanger (NCX) proteins mediate Ca2+-fluxes across the cell membrane to maintain Ca2+ homeostasis in many cell types. Eukaryotic NCX contains Ca2+-binding regulatory domains, CBD1 and CBD2. Ca2+ binding to a primary sensor (Ca3-Ca4 sites) on CBD1 activates mammalian NCXs, whereas CALX, a Drosophila NCX ortholog, displays an inhibitory response to regulatory Ca2+. To further elucidate the underlying regulatory mechanisms, we determined the 2.7 Å crystal structure of mammalian CBD12-E454K, a two-domain construct that retains wild-type properties. In conjunction with stopped-flow kinetics and SAXS (small-angle X-ray scattering) analyses of CBD12 mutants, we show that Ca2+ binding to Ca3-Ca4 sites tethers the domains via a network of interdomain salt-bridges. This Ca2+-driven interdomain switch controls slow dissociation of “occluded” Ca2+ from the primary sensor and thus dictates Ca2+ sensing dynamics. In the Ca2+-bound conformation, the interdomain angle of CBD12 is very similar in NCX and CALX, meaning that the interdomain distances cannot account for regulatory diversity in NCX and CALX. Since the two-domain interface is nearly identical among eukaryotic NCXs, including CALX, we suggest that the Ca2+-driven interdomain switch described here represents a general mechanism for initial conduction of regulatory signals in NCX variants

Chemistry and the Science of Transformation in Mary Shelley’s Frankenstein

This essay reads the novel in a new way, examining the way that Victor Frankenstein's chemical education (he does not train to be a doctor!) enables his creation of the monster. It reveals that chemists of the period had a different worldview to others where they saw the world in constant transformation and flux. I have written this essay co-written the introduction to the special issue, and co-edited the whole

Multi-Objective Clean Take-Off Flight Paths for Civil Aircraft

International audienceno abstrac

Improved 3D Coastal Outcrop Models Using Multiple UAV Acquisitions: Example of the Hikurangi Margin, New Zealand

International audienceThe investigation of outcrop analogues using Unmanned Aerial Vehicle (UAV) has become increasingly popular to improve the understanding of subsurface heterogeneity. Although seismic data offer an invaluable method to characterize the stratigraphic architecture of deep-water systems and therefore help unlock their reservoir potential, the scale of observations cannot capture detailed vertical extent of the sediment distribution and the related processes responsible for the deposits. This work uses a combination of photographic data acquired from a UAV using Ground Control Points, and traditional fieldwork data to better characterize the gravity-driven systems of the Hikurangi subduction wedge (North Island, New Zealand). Their best onshore expressions are found along the coastline: a challenging working environment which evolves every day leading to multiple acquisitions (tides will affect wind variation and wave action, impacting sand coverage; sun and clouds will impact light exposure). It is therefore essential to adapt the way we acquire and model data to ensure that all the information are gathered into one single comprehensive model. Our study proposes to expand on the traditional Structure from Motion workflow to account for such settings and help create more accurate models. We will present this approach applied to three different coastal outcrops. \textcopyright EAGE 2019

Improved 3D Coastal Outcrop Models Using Multiple UAV Acquisitions: Example of the Hikurangi Margin, New Zealand

International audienceThe investigation of outcrop analogues using Unmanned Aerial Vehicle (UAV) has become increasingly popular to improve the understanding of subsurface heterogeneity. Although seismic data offer an invaluable method to characterize the stratigraphic architecture of deep-water systems and therefore help unlock their reservoir potential, the scale of observations cannot capture detailed vertical extent of the sediment distribution and the related processes responsible for the deposits. This work uses a combination of photographic data acquired from a UAV using Ground Control Points, and traditional fieldwork data to better characterize the gravity-driven systems of the Hikurangi subduction wedge (North Island, New Zealand). Their best onshore expressions are found along the coastline: a challenging working environment which evolves every day leading to multiple acquisitions (tides will affect wind variation and wave action, impacting sand coverage; sun and clouds will impact light exposure). It is therefore essential to adapt the way we acquire and model data to ensure that all the information are gathered into one single comprehensive model. Our study proposes to expand on the traditional Structure from Motion workflow to account for such settings and help create more accurate models. We will present this approach applied to three different coastal outcrops. \textcopyright EAGE 2019