Featured
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Article
| Open Access
Neoantigen quality predicts immunoediting in survivors of pancreatic cancer
The human immune system naturally edits cancers of high-quality neoantigens.
- Marta Łuksza
- , Zachary M. Sethna
- & Vinod P. Balachandran
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Structural basis of lipopolysaccharide maturation by the O-antigen ligase
Cryo-electron microscopy structures of the bacterial O-antigen ligase WaaL, combined with genetics, biochemistry and molecular dynamics simulations, provide insight into the mechanism by which WaaL catalyses the biosynthesis of lipopolysaccharide.
- Khuram U. Ashraf
- , Rie Nygaard
- & Filippo Mancia
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A backbone-centred energy function of neural networks for protein design
Modelling by SCUBA of the backbone-centred energy surface extends the diversity of designable proteins.
- Bin Huang
- , Yang Xu
- & Haiyan Liu
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Article
| Open Access
Highly accurate protein structure prediction with AlphaFold
AlphaFold predicts protein structures with an accuracy competitive with experimental structures in the majority of cases using a novel deep learning architecture.
- John Jumper
- , Richard Evans
- & Demis Hassabis
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Article |
Structural basis of omega-3 fatty acid transport across the blood–brain barrier
Cryo-electron microscopy and molecular dynamics simulations reveal how MFSD2A transports essential omega-3 fatty acids across the blood–brain and blood–retina barriers as lysolipids.
- Rosemary J. Cater
- , Geok Lin Chua
- & Filippo Mancia
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Bacterial coexistence driven by motility and spatial competition
In mixed bacterial populations that colonize nutrient patches, a growth–migration trade-off can lead to spatial exclusion that provides an advantage to populations that become rare, thereby stabilizing the community.
- Sebastian Gude
- , Erçağ Pinçe
- & Sander J. Tans
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Letter |
Heterochromatin drives compartmentalization of inverted and conventional nuclei
Attractions between heterochromatic regions are essential for phase separation of the active and inactive genome in inverted and conventional nuclei, whereas chromatin–lamina interactions are necessary to build the conventional genomic architecture from these segregated phases.
- Martin Falk
- , Yana Feodorova
- & Leonid A. Mirny
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Structure of native lens connexin 46/50 intercellular channels by cryo-EM
Cryo-electron microscopy structures of connexin channels composed of connexin 46 and connexin 50 in an open-state reveal features that govern permselectivity and the location of mutated residues linked to herediatry cataracts.
- Janette B. Myers
- , Bassam G. Haddad
- & Steve L. Reichow
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Letter |
Molecular mechanism of GPCR-mediated arrestin activation
Molecular dynamics simulations and site-directed fluorescence spectroscopy show that the transmembrane core and cytoplasmic tail of G-protein-coupled receptors independently and cooperatively activate arrestin.
- Naomi R. Latorraca
- , Jason K. Wang
- & Ron O. Dror
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Letter |
A tethering complex drives the terminal stage of SNARE-dependent membrane fusion
Tethering proteins, known to mediate initial recognition and attachment during membrane fusion, are essential for driving the transition from the hemifused state to fusion pore formation.
- Massimo D’Agostino
- , Herre Jelger Risselada
- & Andreas Mayer
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Letter |
A neoantigen fitness model predicts tumour response to checkpoint blockade immunotherapy
An immune fitness model for tumours under checkpoint blockade immunotherapy is proposed, through which the authors show that the presentation and recognition properties of dominant neoantigens distributed over tumour subclones are predictive of response in melanoma and lung cancer cohorts.
- Marta Łuksza
- , Nadeem Riaz
- & Benjamin D. Greenbaum
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Letter |
A novel mechanism for mechanosensory-based rheotaxis in larval zebrafish
In the absence of visual information, larval zebrafish (Danio rerio) use their mechanosensory lateral line to perform rheotaxis by using flow velocity gradients as navigational cues.
- Pablo Oteiza
- , Iris Odstrcil
- & Florian Engert
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Article |
A living mesoscopic cellular automaton made of skin scales
A mesoscopic cellular automaton arising from a microscopic reaction–diffusion system as a function of skin thickness is observed in ocellated lizards, showing that cellular automata are not merely abstract computational systems, but can directly correspond to processes generated by biological evolution.
- Liana Manukyan
- , Sophie A. Montandon
- & Michel C. Milinkovitch
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Letter |
Asymmetric division of contractile domains couples cell positioning and fate specification
Here, a combination of biophysical measurement, modelling, and genetic and experimental manipulation of cell contractile components is used to analyse the formation of the inner cell mass in the early mouse embryo.
- Jean-Léon Maître
- , Hervé Turlier
- & Takashi Hiiragi
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Letter |
A spatial model predicts that dispersal and cell turnover limit intratumour heterogeneity
A new model of tumour evolution is presented to explain how short-range migration and cell turnover within the tumour can provide the basic environment of rapid cell mixing, allowing even a small selective advantage to dominate the mass within relevant time frames.
- Bartlomiej Waclaw
- , Ivana Bozic
- & Martin A. Nowak
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Letter |
Structural basis for modulation of a G-protein-coupled receptor by allosteric drugs
Binding modes and molecular mechanisms of several allosteric modulators of a prototypical G-protein-coupled receptor are revealed using atomic-level simulations and validated by the rational design of a modulator with substantially altered effects.
- Ron O. Dror
- , Hillary F. Green
- & David E. Shaw
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Letter |
Bacterial virulence proteins as tools to rewire kinase pathways in yeast and immune cells
Virulence factors from two bacteria are used to reprogram intracellular signalling in yeast and immune T cells, illustrating how pathogens can provide a toolkit to engineer cells for biotechnological or therapeutic applications.
- Ping Wei
- , Wilson W. Wong
- & Wendell A. Lim
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Letter |
Live-cell delamination counterbalances epithelial growth to limit tissue overcrowding
To maintain homeostasis in epithelial cell layers in Drosophila, cell overcrowding causes a proportion of cells to undergo a loss of cell adhesive junctions and be squeezed out by neighbouring cells.
- Eliana Marinari
- , Aida Mehonic
- & Buzz Baum
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Article |
Neuronal filtering of multiplexed odour representations
Optogenetic stimulation in the zebrafish olfactory bulb and downstream read out of activity in the homologue of olfactory cortex demonstrate how temporal filtering can extract specific components of neuronal codes.
- Francisca Blumhagen
- , Peixin Zhu
- & Rainer W. Friedrich
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Letter |
Distributed biological computation with multicellular engineered networks
For synthetic biologists' creativity to be unleashed, basic circuits must become truly interchangeable, that is, modular and scalable. This study, one of two linked papers, has harnessed yeast pheromone communication to achieve complex computation through communication between individual cells performing simple logic functions. Such extracellular 'chemical wiring' is one promising way to get around intracellular noise when building more complex genetic circuitry.
- Sergi Regot
- , Javier Macia
- & Ricard Solé
The structure and physical properties of a packaged bacteriophage particle