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Inside-out receptor inhibition p.344

Structures of two chemokine receptor proteins in complex with small molecules reveal a previously unknown binding pocket that could be a drug target for treating a range of diseases involving this receptor family. See Letters p.458 & p.462

Thomas P. Sakmar & Thomas Huber

doi: 10.1038/nature20486

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A radical change in enzyme catalysis p.345

A method has been devised that allows a ketoreductase enzyme to catalyse reactions other than its natural ones. The key is to excite the enzyme's cofactor using light – an approach that might work for other enzymes. See Letter p.414

Uwe T. Bornscheuer

doi: 10.1038/540345a

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A gene-expression profile for leukaemia p.346

Can simple genetic risk profiles be identified for complex diseases? The development of a gene-expression profile for acute myeloid leukaemia suggests that they can, and that they may improve prognosis prediction. See Letter p.433

Gerrit J. Schuurhuis

doi: 10.1038/nature20488

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The dynamics of Earth's surface water p.348

High-resolution satellite mapping of Earth's surface water during the past 32 years reveals changes in the planet's water systems, including the influence of natural cycles and human activities. See Letter p.418

Dai Yamazaki & Mark A. Trigg

doi: 10.1038/nature21100

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Cause and consequence in aged-muscle decline p.349

Activation of aged muscle stem cells induces changes in DNA packaging that lead to expression of the gene Hoxa9. This reactivates embryonic signalling pathways, restricting the cells' ability to repair injured muscle. See Letter p.428

Susan Eliazer & Andrew S. Brack

doi: 10.1038/nature20485

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An eye on retinal recovery p.350

Retinal-cell transplants restore vision in mouse models of retinal degeneration. It emerges that the transplant leads to an exchange of material between donor and host cells — not to donor-cell integration into the retina, as had been presumed.

Michael A. Dyer

doi: 10.1038/nature20487

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Articles

The seahorse genome and the evolution of its specialized morphology p.395

Here, the genome sequence of the tiger tail seahorse is reported and comparative genomic analyses with other ray-finned fishes are used to explore the genetic basis of the unique morphology and reproductive system of the seahorse.

Qiang Lin, Shaohua Fan, Yanhong Zhang, Meng Xu, Huixian Zhang, Yulan Yang, Alison P. Lee, Joost M. Woltering, Vydianathan Ravi, Helen M. Gunter + et al.

doi: 10.1038/nature20595

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Electric-field-stimulated protein mechanics p.400

A new method in which strong electric fields are applied to a protein crystal while collecting time-resolved X-ray diffraction patterns is able to follow the mechanical motions of all the constituent atoms, with implications for molecular biology and drug discovery.

Doeke R. Hekstra, K. Ian White, Michael A. Socolich, Robert W. Henning, Vukica Šrajer & Rama Ranganathan

doi: 10.1038/nature20571

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Letters

Genome-wide changes in lncRNA, splicing, and regional gene expression patterns in autism p.423

Gene expression analysis in brain tissue from individuals with and without autism spectrum disorder (ASD) suggests that the transcription factor SOX5 contributes to an ASD-associated reduction in transcriptional differences between brain areas and indicates that common transcriptomic changes occur in different forms of ASD.

Neelroop N. Parikshak, Vivek Swarup, T. Grant Belgard, Manuel Irimia, Gokul Ramaswami, Michael J. Gandal, Christopher Hartl, Virpi Leppa, Luis de la Torre Ubieta, Jerry Huang + et al.

doi: 10.1038/nature20612

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Epigenetic stress responses induce muscle stem-cell ageing by Hoxa9 developmental signals p.428

Changes in active chromatin marks in old activated satellite cells lead to Hoxa9 activation, which induces the expression of developmental pathway genes with a known inhibitory effect on satellite cell function and muscle regeneration in aged mice.

Simon Schwörer, Friedrich Becker, Christian Feller, Ali H. Baig, Ute Köber, Henriette Henze, Johann M. Kraus, Beibei Xin, André Lechel, Daniel B. Lipka + et al.

doi: 10.1038/nature20603

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A 17-gene stemness score for rapid determination of risk in acute leukaemia p.433

A rapid gene signature test (LSC17) that captures stem cell expression programs in acute myeloid leukaemia patients at diagnosis is associated with therapy response and survival, facilitating initial treatment stratification.

Stanley W. K. Ng, Amanda Mitchell, James A. Kennedy, Weihsu C. Chen, Jessica McLeod, Narmin Ibrahimova, Andrea Arruda, Andreea Popescu, Vikas Gupta, Aaron D. Schimmer + et al.

doi: 10.1038/nature20598

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Zika virus infection damages the testes in mice p.438

Infection of male mice with Zika virus caused testicular and epididymal damage, reduction in sex hormone levels, destruction of germ and somatic cells in the testis, loss of mature sperm and reduction in fertility.

Jennifer Govero, Prabagaran Esakky, Suzanne M. Scheaffer, Estefania Fernandez, Andrea Drury, Derek J. Platt, Matthew J. Gorman, Justin M. Richner, Elizabeth A. Caine, Vanessa Salazar + et al.

doi: 10.1038/nature20556

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Receptor usage dictates HIV-1 restriction by human TRIM5α in dendritic cell subsets p.448

The most prevalent route of HIV-1 infection is across mucosal tissues after sexual contact. Langerhans cells (LCs) belong to the subset of dendritic cells (DCs) that line the mucosal epithelia of vagina and foreskin and have the ability to sense and induce immunity to invading pathogens. Anatomical and functional characteristics make LCs one of the primary targets of HIV-1 infection. Notably, LCs form a protective barrier against HIV-1 infection and transmission. LCs restrict HIV-1 infection through the capture of HIV-1 by the C-type lectin receptor Langerin and subsequent internalization into Birbeck granules. However, the underlying molecular mechanism of HIV-1 restriction in LCs remains unknown. Here we show that human E3-ubiquitin ligase tri-partite-containing motif 5α (TRIM5α) potently restricts HIV-1 infection of LCs but not of subepithelial DC-SIGN+ DCs. HIV-1 restriction by TRIM5α was thus far considered to be reserved to non-human primate TRIM5α orthologues, but our data strongly suggest that human TRIM5α is a cell-specific restriction factor dependent on C-type lectin receptor function. Our findings highlight the importance of HIV-1 binding to Langerin for the routeing of HIV-1 into the human TRIM5α-mediated restriction pathway. TRIM5α mediates the assembly of an autophagy-activating scaffold to Langerin, which targets HIV-1 for autophagic degradation and prevents infection of LCs. By contrast, HIV-1 binding to DC-SIGN+ DCs leads to disassociation of TRIM5α from DC-SIGN, which abrogates TRIM5α restriction. Thus, our data strongly suggest that restriction by human TRIM5α is controlled by C-type-lectin-receptor-dependent uptake of HIV-1, dictating protection or infection of human DC subsets. Therapeutic interventions that incorporate C-type lectin receptors and autophagy-targeting strategies could thus provide cell-mediated resistance to HIV-1 in humans.

Carla M. S. Ribeiro, Ramin Sarrami-Forooshani, Laurentia C. Setiawan, Esther M. Zijlstra-Willems, John L. van Hamme, Wikky Tigchelaar, Nicole N. van der Wel, Neeltje A. Kootstra, Sonja I. Gringhuis & Teunis B. H. Geijtenbeek

doi: 10.1038/nature20567

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Structure of photosystem II and substrate binding at room temperature p.453

The structures of three intermediate states of photosystem II, which is crucial for photosynthesis, have been solved at room temperature, shedding new light on this process.

Iris D. Young, Mohamed Ibrahim, Ruchira Chatterjee, Sheraz Gul, Franklin D. Fuller, Sergey Koroidov, Aaron S. Brewster, Rosalie Tran, Roberto Alonso-Mori, Thomas Kroll + et al.

doi: 10.1038/nature20161

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Structure of CC chemokine receptor 2 with orthosteric and allosteric antagonists p.458

The crystal structure of CCR2 chemokine receptor in a complex with two different antagonists—one orthosteric the other allosteric—which functionally cooperate to inhibit CCR2.

Yi Zheng, Ling Qin, Natalia V. Ortiz Zacarías, Henk de Vries, Gye Won Han, Martin Gustavsson, Marta Dabros, Chunxia Zhao, Robert J. Cherney, Percy Carter + et al.

doi: 10.1038/nature20605

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