Folate metabolism is intricately linked to purine de novo synthesis through the incorporation of folate-derived one-carbon units into the purine scaffold. By investigating chemical and genetic depende...

Nature Structural & Molecular Biology, Published online: 28 October 2025; doi:10.1038/s41594-025-01698-zThe structural biology community in New York City combines expertise and access to cutting-edge instrumentation that fosters cooperation. Working collaboratively is indispensable because developing interdisciplinary tools can enable discoveries in cell, structural and molecular biology.

Design of modular, transferable protein assemblies has broad applicability and in structural biology could help with the ever-troublesome crystallization bottleneck, including finding robustly behaved protein crystals for rapidly characterizing ligands or drug candidates or generating multiple polymorphs to illuminate diverse conformations. Nanobodies as crystallization chaperones are well-established but still unreliable, as we show here. Instead, we show an exemplar of how robust crystallization behavior can be engineered by exploring many combinations (>200) of nanobody surface mutations over several iterations. Critically, what needed testing was crystallization and diffraction quality, since target–nanobody binding affinity is decoupled from crystallizability enhancement. Our study yielded multiple polymorphs, all mediated by the same interface, with dramatically improved resolution and diffraction reliability for some mutants; we thus name them ‘Gluebodies’ (Gbs). We further demonstrate that these Gb mutations do transfer to some other targets, both for achieving robust crystallization in alternative packing forms and for establishing the ability to crystallize a key early stage readout. Since the Gb interface is evidently a favored interaction, it may be broadly applicable for modular assembly; more specifically, this work suggests that Gbs should be routinely attempted for crystallization whenever nanobodies are available.

Dr Naomi Pollock

The transport of amino acids across cell membranes is essential for metabolism, neuronal signalling, and immune system function. The amino acid polyamine organocation (APC) superfamily regulates amino...

Antibiotic resistance is among the greatest threats of the modern era. Multidrug efflux pumps expel antibiotics from bacterial cells and present a particular challenge by conferring resistance to a br...

The SLC45A4 gene encodes a neuronal polyamine transporter and is linked to pain response in humans and mice.

Disulfide-based dimerization of modified identical and heterologous nanobody scaffolds enables higher-order assembly for high-resolution cryo-electron microscopy structure determination that is widely...

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Functional and mechanistic analysis of all single–amino acid variants in the human citrate transporter SLC13A5.