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Planetary scienceGalvanized lunacy p.346

The finding that magmatic material from the Moon is more enriched in the heavy isotopes of zinc than its terrestrial and Martian analogues prompts fresh thinking about the origin of our natural satellite. See Letter p.376

Tim Elliott

doi: 10.1038/490346a

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Cancer therapyTumours switch to resist p.347

Tumour cells can respond to targeted immune-cell therapies by losing proteins that mark them as being cancerous. Subverting this resistance mechanism may lead to more durable cancer-treatment strategies. See Letter p.412

Antoni Ribas & Paul C. Tumeh

doi: 10.1038/nature11489

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Structural biologyBundles of insights into sugar transporters p.348

The structure of a bacterial protein belonging to the 'sugar porter' family guides the building of long-sought molecular models of proteins that transport glucose across cell membranes in humans. See Article p.361

Peter J. F. Henderson & Stephen A. Baldwin

doi: 10.1038/490348a

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HIVDesign by trial p.350

A genetic analysis of viruses infecting participants in an HIV vaccine trial indicates that the vaccine is more protective against viruses that have variations at specific sites in the viral envelope. See Letter p.417

David V. Glidden

doi: 10.1038/490350a

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Molecular biologyChoose your protein partners p.351

A large-scale study sheds light on the extraordinary molecular-recognition skills of the chaperone HSP90, which allow this protein to interact selectively with hundreds of other proteins of diverse function.

Rahul S. Samant & Paul Workman

doi: 10.1038/490351a

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EcologyThe big picture of marsh loss p.352

A landscape-scale experiment shows that excessive nutrient levels can cause the loss of salt marshes — a result that was not seen in smaller studies. This illustrates the value of large-scale, long-term studies in ecology. See Letter p.388

Steven C. Pennings

doi: 10.1038/490352a

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Articles

The aged niche disrupts muscle stem cell quiescence p.355

The niche is a conserved regulator of stem cell quiescence and function. During ageing, stem cell function declines. To what extent and by what means age-related changes within the niche contribute to this phenomenon are unknown. Here we demonstrate that the aged muscle stem cell niche, the muscle fibre, expresses Fgf2 under homeostatic conditions, driving a subset of satellite cells to break quiescence and lose their self-renewing capacity. We show in mice that relatively dormant aged satellite cells robustly express sprouty 1 (Spry1), an inhibitor of fibroblast growth factor (FGF) signalling. Increasing FGF signalling in aged satellite cells under homeostatic conditions by removing Spry1 results in the loss of quiescence, satellite cell depletion and diminished regenerative capacity. Conversely, reducing niche-derived FGF activity through inhibition of Fgfr1 signalling or overexpression of Spry1 in satellite cells prevents their depletion. These experiments identify an age-dependent change in the stem cell niche that directly influences stem cell quiescence and function.

Joe V. Chakkalakal, Kieran M. Jones, M. Albert Basson & Andrew S. Brack

doi: 10.1038/nature11438

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Crystal structure of a bacterial homologue of glucose transporters GLUT1–4 p.361

Glucose transporters are essential for metabolism of glucose in cells of diverse organisms from microbes to humans, exemplified by the disease-related human proteins GLUT1, 2, 3 and 4. Despite rigorous efforts, the structural information for GLUT1–4 or their homologues remains largely unknown. Here we report three related crystal structures of XylE, an Escherichia coli homologue of GLUT1–4, in complex with d-xylose, d-glucose and 6-bromo-6-deoxy-d-glucose, at resolutions of 2.8, 2.9 and 2.6 Å, respectively. The structure consists of a typical major facilitator superfamily fold of 12 transmembrane segments and a unique intracellular four-helix domain. XylE was captured in an outward-facing, partly occluded conformation. Most of the important amino acids responsible for recognition of d-xylose or d-glucose are invariant in GLUT1–4, suggesting functional and mechanistic conservations. Structure-based modelling of GLUT1–4 allows mapping and interpretation of disease-related mutations. The structural and biochemical information reported here constitutes an important framework for mechanistic understanding of glucose transporters and sugar porters in general.

Linfeng Sun, Xin Zeng, Chuangye Yan, Xiuyun Sun, Xinqi Gong, Yu Rao & Nieng Yan

doi: 10.1038/nature11524

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Structure of AMP-PNP-bound vitamin B12 transporter BtuCD–F p.367

The ATP-binding cassette (ABC) transporter BtuCD mediates the uptake of vitamin B12 across the inner membrane of Escherichia coli. Previous structures have shown the conformations of apo states, but the transport mechanism has remained unclear. Here we report the 3.5 Å crystal structure of the transporter-binding protein complex BtuCD–BtuF (BtuCD–F) trapped in an β-γ-imidoadenosine 5′-phosphate (AMP-PNP)-bound intermediate state. Although the ABC domains (BtuD subunits) form the expected closed sandwich dimer, the membrane-spanning BtuC subunits adopt a new conformation, with the central translocation pathway sealed by a previously unrecognized cytoplasmic gate. A fully enclosed cavity is thus formed approximately halfway across the membrane. It is large enough to accommodate a vitamin B12 molecule, and radioligand trapping showed that liposome-reconstituted BtuCD–F indeed contains bound B12 in the presence of AMP-PNP. In combination with engineered disulphide crosslinking and functional assays, our data suggest an unexpected peristaltic transport mechanism that is distinct from those observed in other ABC transporters.

Vladimir M. Korkhov, Samantha A. Mireku & Kaspar P. Locher

doi: 10.1038/nature11442

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Letters

Increased HIV-1 vaccine efficacy against viruses with genetic signatures in Env V2 p.417

Morgane Rolland, Paul T. Edlefsen, Brendan B. Larsen, Sodsai Tovanabutra, Eric Sanders-Buell, Tomer Hertz, Allan C. deCamp, Chris Carrico, Sergey Menis, Craig A. Magaret + et al.

doi: 10.1038/nature11519

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