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A zinc-sensing protein gives flies a gut feeling for growth 期刊论文
NATURE, 2020, 580 (7802)
作者:  Heffernan, Olive
收藏  |  浏览/下载：7/0  |  提交时间：2020/07/03

A zinc-sensing ion channel, Hodor, has now been found in the intestine of fruit flies. Hodor activates the TORC1 signalling pathway, and in doing so, influences organism-wide growth and metabolism.


  
An intestinal zinc sensor regulates food intake and developmental growth 期刊论文
NATURE, 2020, 580 (7802) : 263-+
作者:  Wu, Thomas D.;  39;Gorman, William E.
收藏  |  浏览/下载：14/0  |  提交时间：2020/07/03

Hodor, an intestinal zinc-gated chloride channel, controls systemic growth in Drosophila by promoting food intake and by modulating Tor signalling and lysosomal homeostasis within enterocytes.


In cells, organs and whole organisms, nutrient sensing is key to maintaining homeostasis and adapting to a fluctuating environment(1). In many animals, nutrient sensors are found within the enteroendocrine cells of the digestive system  however, less is known about nutrient sensing in their cellular siblings, the absorptive enterocytes(1). Here we use a genetic screen in Drosophila melanogaster to identify Hodor, an ionotropic receptor in enterocytes that sustains larval development, particularly in nutrient-scarce conditions. Experiments in Xenopus oocytes and flies indicate that Hodor is a pH-sensitive, zinc-gated chloride channel that mediates a previously unrecognized dietary preference for zinc. Hodor controls systemic growth from a subset of enterocytes-interstitial cells-by promoting food intake and insulin/IGF signalling. Although Hodor sustains gut luminal acidity and restrains microbial loads, its effect on systemic growth results from the modulation of Tor signalling and lysosomal homeostasis within interstitial cells. Hodor-like genes are insect-specific, and may represent targets for the control of disease vectors. Indeed, CRISPR-Cas9 genome editing revealed that the single hodor orthologue in Anopheles gambiae is an essential gene. Our findings highlight the need to consider the instructive contributions of metals-and, more generally, micronutrients-to energy homeostasis.


  
Constructing protein polyhedra via orthogonal chemical interactions 期刊论文
NATURE, 2020, 578 (7793) : 172-+
作者:  Mooley, K. P.;  Deller, A. T.;  Gottlieb, O.;  Nakar, E.;  Hallinan, G.;  Bourke, S.;  Frail, D. A.;  Horesh, A.;  Corsi, A.;  Hotokezaka, K.
收藏  |  浏览/下载：7/0  |  提交时间：2020/07/03

Many proteins exist naturally as symmetrical homooligomers or homopolymers(1). The emergent structural and functional properties of such protein assemblies have inspired extensive efforts in biomolecular design(2-5). As synthesized by ribosomes, proteins are inherently asymmetric. Thus, they must acquire multiple surface patches that selectively associate to generate the different symmetry elements needed to form higher-order architectures(1,6)-a daunting task for protein design. Here we address this problem using an inorganic chemical approach, whereby multiple modes of protein-protein interactions and symmetry are simultaneously achieved by selective, '  one-pot'  coordination of soft and hard metal ions. We show that a monomeric protein (protomer) appropriately modified with biologically inspired hydroxamate groups and zinc-binding motifs assembles through concurrent Fe3+ and Zn2+ coordination into discrete dodecameric and hexameric cages. Our cages closely resemble natural polyhedral protein architectures(7,8) and are, to our knowledge, unique among designed systems(9-13) in that they possess tightly packed shells devoid of large apertures. At the same time, they can assemble and disassemble in response to diverse stimuli, owing to their heterobimetallic construction on minimal interprotein-bonding footprints. With stoichiometries ranging from [2 Fe:9 Zn:6 protomers] to [8 Fe:21 Zn:12 protomers], these protein cages represent some of the compositionally most complex protein assemblies-or inorganic coordination complexes-obtained by design.


An inorganic chemical approach to biomolecular design is used to generate '  cages'  that can simultaneously promote symmetry and multiple modes of protein interactions.