I10-Beamline for Advanced Dichroism - scattering
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Duncan
Miertschin
,
Sundar
Kunwar
,
Balaram
Regmi
,
Poshan
Kandel
,
Sanjib
Thapa
,
Davis
Crater
,
Luca
Basso
,
Adam
Dodson
,
Zheng
Gai
,
Lide
Yao
,
Yu-Wei
Chen
,
Peter
Bencok
,
Armin
Kleibert
,
Yen-Lin
Huang
,
Andy
Mounce
,
Paul G.
Kotula
,
Sebastiaan
Van Dijken
,
Alessandro R.
Mazza
,
Thomas Z.
Ward
,
Nick
Shepelin
,
Alan
Farhan
Diamond Proposal Number(s):
[40992]
Open Access
Abstract: Multiferroics that combine ferroelectricity and magnetic order are attractive for electronic and spintronic technologies, yet chemical disorder that promotes relaxor ferroelectricity usually suppresses long-range magnetic order. Here, we report entropy-stabilized relaxor multiferroicity in epitaxial hexagonal (Tb0.2Dy0.2Ho0.2Lu0.2Yb0.2)FeO3 thin films. Structural, magnetic, dielectric, and synchrotron spectroscopic measurements show the coexistence of relaxor ferroelectricity and long-range ferromagnetic order. We find that improper ferroelectricity remains robust against A-site configurational disorder, while the Fe sublattice preserves magnetic exchange. This separation of the microscopic origins of the polar and magnetic responses enables chemically disordered multiferroicity. Our results establish entropy engineering in hexagonal ferrites as a route toward multifunctional oxide thin films and provide a general design strategy for high-entropy multiferroics.
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Sep 2026
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DIAD-Dual Imaging and Diffraction Beamline
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Diamond Proposal Number(s):
[41953]
Open Access
Abstract: The development of efficient recycling processes for lithium-ion battery electrode materials is essential for sustainable battery technologies. TiNb2O7 (TNO) is an attractive high-power anode material, but recycling strategies remain largely unexplored. Here, we report a direct recycling approach for TNO anodes recovered from a cycled TNO/LiNi0.6Mn0.2Co0.2O2 cell. We find that residual lithium in recovered TNO promotes the formation of a lithiated rutile impurity phase and Ti2Nb10O29 during thermal processing, which degrades the electrochemical performance of the recovered TNO. Structural and compositional analyses reveal the origin of these phases and guide the development of a recycling route that combines hydrothermal lithium removal with a subsequent heat treatment, preventing impurity formation. Recycled TNO produced by this method delivers high capacity, excellent rate capability, and stable performance at high current densities, achieving 279 (5) and 261 (10) mA h g−1 at 2 and 4 A g−1, respectively, comparable to commercial TNO. These results demonstrate a viable direct recycling strategy for TNO anodes.
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Sep 2026
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I04-Macromolecular Crystallography
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Diamond Proposal Number(s):
[34035]
Open Access
Abstract: The rapidly accelerated fibrosarcoma/mitogen-activated protein kinase kinase/extracellular signal-regulated kinase (RAF/MEK/ERK) signaling cascade regulates cell proliferation and differentiation and is frequently dysregulated in cancer. Approximately 90% of RAF-mutant cancers harbor mutations in B-type rapidly accelerated fibrosarcoma (BRAF). Its proto-oncogenicity is attributed to a four-residue N-terminal acidic (NtA) motif. Although a long-standing model proposes that the NtA promotes activating asymmetric RAF dimerization, the model lacks structural support. Here, we present structures of NtA-mediated asymmetric BRAF dimers bound to their substrate MEK1. Cellular and biochemical data show that the NtA is not required for KRAS-mediated BRAF recruitment to the plasma membrane but is required for the fully catalytically active state. The structure capturing BRAF in a post-catalytic state bound to Ser222-phosphorylated MEK1 further supports this model. The combination of structural and cellular data corroborates the model of NtA-driven asymmetry in BRAF activation and resolves a long-standing disconnect between RAF cancer genetics and structural biology.
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Aug 2026
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I04-Macromolecular Crystallography
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Jemma K.
Betts
,
Cy M.
Jeffries
,
Tim C.
Passchier
,
Hermia C. Y.
Kung
,
Sarah P.
Graham
,
Mahmoud A. S.
Abdelhamid
,
Jamieson A. I.
Howard
,
Timothy D.
Craggs
,
Stephen C.
Graham
,
Ian
Brierley
,
Mark C.
Leake
,
Steven D.
Quinn
,
Chris H.
Hill
Diamond Proposal Number(s):
[32736]
Abstract: Programmed −1 ribosomal frameshifting (PRF) is a translational control mechanism used by RNA viruses to regulate the relative abundance of proteins encoded in different reading frames. Cardioviruses exhibit the highest known PRF efficiency, with ∼85% of ribosomes shifting into the −1 frame. This unusual event requires an interaction between the viral 2A protein and a stimulatory element in the RNA genome, but the basis for protein dependence is unclear. To address this, here we investigate the structure and dynamics of the PRF signal in Theiler’s murine encephalitis virus (TMEV). By combining X-ray crystallography, small-angle X-ray scattering (SAXS), and single-molecule fluorescence resonance energy transfer (smFRET), we show that 2A binding switches the RNA from a stem-loop conformation into a pseudoknot, and we demonstrate that pseudoknot formation is essential for efficient PRF in vitro and in cells. Together, these findings illustrate how the cardiovirus PRF element behaves as a protein-dependent riboswitch, defining the molecular mechanism by which frameshifting is conditionally activated.
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Aug 2026
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Krios I-Titan Krios I at Diamond
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Carys
Williams
,
Laura M.
Nocka
,
George
Hedger
,
Pragya
Parashara
,
Els
Pardon
,
Naomi R.
Latorraca
,
Ganesh V.
Pusapati
,
Parijat
Sarkar
,
Dorothy
Lartey
,
Lei
Gao
,
Ljiljana
Milenkovic
,
Rod
Chalk
,
Jan
Steyaert
,
Susan
Marqusee
,
Loic
Carrique
,
J. Fernando
Bazan
,
Sarah L.
Rouse
,
Jennifer H.
Kong
,
Christian
Siebold
,
Rajat
Rohatgi
Diamond Proposal Number(s):
[28713]
Open Access
Abstract: Receptor-type E3 ubiquitin ligases enable extracellular signals to control ubiquitylation in the cytoplasm, playing widespread roles in development, metabolism, and immunity. Using cryoelectron microscopy, integrated with biophysical and functional studies, we visualized a human E3 complex composed of two transmembrane proteins, MEGF8 and MOSMO, and the intracellular RING-family protein MGRN1. This MEGF8-MOSMO-MGRN1 (MMM) complex attenuates Hedgehog signaling by ubiquitylating Smoothened (SMO), a G-protein-coupled receptor (GPCR) that transduces morphogen signals. A long helix in the MMM complex engages SMO using an intramembrane degron and extends into the cytoplasm to suspend an activated and precisely oriented RING domain below the plasma membrane. This architecture enables ubiquitylation of the cytoplasmic surface of SMO, reducing SMO abundance at primary cilia. Our structure provides insights into MEGF8 mutations, which cause multi-organ birth defects, and defines a paradigm for how transmembrane E3 ligases control the cell surface abundance of GPCRs and other signaling receptors.
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Jun 2026
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Krios I-Titan Krios I at Diamond
Krios II-Titan Krios II at Diamond
Krios IV-Titan Krios IV at Diamond
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Diamond Proposal Number(s):
[29812, 34631, 21005]
Open Access
Abstract: RNA polymerase II (RNA Pol II) is central to gene expression, but its catalytic mechanism remains elusive due to the absence of high-resolution structural data. The role of water molecules in RNA Pol II catalysis is unknown. Here, we present 3 high-resolution cryo-electron microscopy structures of active Saccharomyces cerevisiae RNA Pol II elongation complexes in distinct catalytic states: two pre-catalysis states at 1.96 Å and 2.26 Å resolution and a post-catalysis state at 2.33 Å resolution. Each structure contains over 700–1,350 ordered water molecules, many located at functionally critical positions. Comparative analysis shows that these waters play essential roles in proton-transfer steps during RNA Pol II catalysis, facilitating substrate recognition and trigger-loop folding during nucleotide addition. Strikingly, these waters are conserved between prokaryotic and eukaryotic transcription machineries (see Mueller and Darst). These findings provide unprecedented mechanistic insights into RNA Pol II catalysis and reveal vital and evolutionarily conserved roles of water molecules in transcription.
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Apr 2026
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I09-Surface and Interface Structural Analysis
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Muhammad
Ans
,
Eleni
Fiamegkou
,
Ashok S.
Menon
,
Gaurav C.
Pandey
,
Gaolo J.
Paez Fajardo
,
Harry
Gillions
,
Paolo
Melgari
,
Calum
Clenahan
,
Satish
Bolloju
,
Pardeep K.
Thakur
,
Tien-Lin
Lee
,
Serena A.
Cussen
,
Beth I. J.
Johnston
,
Louis F. J.
Piper
Diamond Proposal Number(s):
[38340]
Open Access
Abstract: Lithium nickel oxide (LNO) cathodes offer high capacity for high-energy-density applications but suffer rapid degradation above 4.2 V due to surface and bulk instabilities. Here, we apply an ultrathin aluminum oxide coating using powder atomic layer deposition to improve surface stability. Pouch cell testing shows that coated LNO delivers improved cycling behavior, retaining 91.2% capacity after 100 cycles at C/3. Operando X-ray diffraction reveals that after aging, coated LNO undergoes a less kinetically hindered delithiation, indicating that the surface coating further provides a surface-to-bulk stabilization effect. Postmortem surface sensitive spectroscopy confirms that the aluminum oxide layer (1) scavenges hydrofluoric acid and (2) suppresses surface reconstruction, reducing impedance growth and improving the surface integrity. Overall, the results demonstrate that ultrathin aluminum oxide coatings effectively mitigate interfacial degradation and enhance bulk electrochemical kinetics, providing an effective and scalable approach toward improving the long-term performance of ultra-Ni-rich cathodes.
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Mar 2026
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I03-Macromolecular Crystallography
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Diamond Proposal Number(s):
[36134]
Open Access
Abstract: In contrast to living organisms, viruses were long thought to lack protein synthesis machinery and instead depend on host factors to translate viral transcripts. Here, we discover that giant DNA viruses encode a distinct and functional IF4F translation-initiation complex to drive protein synthesis, thereby blurring the line between cellular and acellular biology. During infection, eukaryotic IF4F on host ribosomes is replaced by an essential viral IF4F that regulates viral translation, virion formation, and replication plasticity during altered host states. Structural dissection of viral IF4F reveals that the mRNA cap-binding subunit mediates exclusive interactions with viral mRNAs, constituting a molecular switch from translating host to viral proteins. Thus, our study establishes that viruses express a eukaryotic translation-initiation complex for protein synthesis, illuminating a series of evolutionary innovations in a core process of life.
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Mar 2026
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Krios III-Titan Krios III at Diamond
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Diamond Proposal Number(s):
[33230, 39228]
Open Access
Abstract: Adeno-associated viruses (AAVs) are parvoviruses utilized as gene therapy vectors. However, the AAV packaging mechanism is unresolved at the molecular level, creating a bottleneck for vector manufacturing, safety, and efficacy. Here, cryo-EM structures of the Rep helicase packaging motor in complex with the packaging marker DNA (ITR) and the Rep-AAV8 capsid complex are presented. Rep-ITR complexes reveal dynamic oligomeric states on the DNA, elucidating the strand separation mechanism coupled to its ATPase cycle. We observe Rep preferentially bound to empty capsids, with a binding interface likely conserved across the virus family. This complex also unveils a cryptic capsid ATP-binding site which, alongside Rep binding, triggers structural rearrangements priming the capsid for packaging. Collectively, these findings advance the understanding of Rep-mediated packaging, with significant implications for parvovirus virology and viral vector design.
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Mar 2026
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I03-Macromolecular Crystallography
I04-Macromolecular Crystallography
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Diamond Proposal Number(s):
[36097]
Open Access
Abstract: The cavity-creating p53 cancer mutation Y220C, which accounts for an estimated 125,000 new cancer cases per year, serves as an excellent paradigm for the development of mutant p53 reactivators. Several molecules that reactivate this thermolabile cancer mutant by targeting the mutation-induced crevice have been developed, and one of them, rezatapopt, is currently in clinical trials. The less frequently occurring Y220N and Y220S mutations are even more destabilizing than Y220C but create a similar surface crevice, raising the question of whether cancer patients with these mutations might also benefit from rezatapopt treatment. Here, we show that rezatapopt also binds to the Y220N and Y220S mutants, with nanomolar affinity, resulting in a full recovery of wild-type-like stability for the latter. High-resolution crystal structures of all three mutants bound to rezatapopt revealed a conserved binding mode, highlighting key interactions, including multipolar interactions of a fluorine substituent at a chiral center with the protein backbone. Consistent with the biophysical and structural data, rezatapopt reactivated p53 signaling in both Y220C and Y220S mutant cells by restoring the folded conformation and transcriptional activity, leading to anti-proliferative effects and apoptosis, albeit requiring higher compound concentrations in Y220S cells. The Y220N mutant, despite exhibiting high-nanomolar affinity for rezatapopt and substantial stabilization, did not show noticeable effects in cells at the concentrations tested, as rezatapopt binding resulted in only partial compensation for the mutation-induced loss of stability, for which we provide a structural explanation. Our data suggest that the development of clinical pan-Y220C/N/S reactivators, which could benefit an additional 10,000 patients per year, is challenging but not impossible.
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Feb 2026
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