All Items
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Abstract:
Mitochondrial transport and distribution are crucial for cellular homeostasis, yet whether and how they are regulated by endoplasmic reticulum (ER)–mitochondria contact sites remains unclear. Here, we demonstrate that the ER protein atlastin-2 (ATL2) orchestrates mitochondrial transport and distribution by promoting assembly of the transport machinery at ER–mitochondria contact sites....
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Endoplasmic reticulum (ER)–mitochondria contact sites facilitate lipid transfer, calcium signaling, and mitochondrial division, yet their role in mitochondrial transport remains unclear. Here, we identify Hereditary Spastic Paraplegia (HSP)-associated protein C19orf12 as an ER-anchored protein that acts as a central organizer for mitochondrial trafficking and rename it EMTOR (ER–Mitochondria...
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Abstract:
The efficacy of immunotherapy in enhancing antitumor immunity in solid tumors remains limited, primarily due to the insufficient immunogenicity of tumor cells. In contrast, vaccination and natural viral infections can generate durable, high-titer antiviral antibodies. A modular Programmed Death-Ligand 1 (PD-L1)-binding antigen presenter (PBAP-gE) has been engineered to tether varicella-zoster...
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Iron (Fe) redox cycling is intricately linked to methane (CH₄) emissions in global wetlands, yet its role under sustained bioturbation remains poorly quantified. We investigated how continuous loach (Misgurnus anguillicaudatus) activity influences CH₄ emissions and Fe dynamics in a ratoon rice system over 178 days. Methane and ecosystem CO₂ fluxes were measured continuously, while in situ...
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Abstract:
The ALKA channel, a member of the Cys-loop ligand-gated ion channel (cysLGIC) family, has recently been identified as a receptor mediating alkaline taste sensation in Drosophila. However, the structure and molecular mechanism underlying pH sensing of ALKA channel remain to be determined. Here, we report the cryo-EM structure of ALKA, determined at a resolution of 2.86 Å under its physiological pH...
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A continuous cost–efficiency spectrum governs brain-wide communication and cognitive reconfiguration
Abstract:Information communication in the brain must balance efficient functional integration with the metabolic and physical costs of long-range connectivity. How this cost–efficiency balance is implemented in large-scale communication networks, and how it adapts across cognitive states and pathology, remains poorly understood. In this study, by systematically tuning the strength of distance constraints...
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Abstract:
The nuclear envelope (NE) plays a crucial role in genome organization by tethering heterochromatin to the nuclear periphery. Yet, how individual NE-associating factors regulate 3D genome architecture remains incompletely understood. Here, we leverage the mitosis-to-G1 phase transition as an experimental system to dissect the roles of Lamin A/C and Lamin B receptor (LBR) in post-mitotic genome...
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Abstract:
Protein evolution in nature and in the laboratory proceeds through incremental, largely undirected mutational steps, restricting exploration to local regions of sequence space and limiting access to remote yet potentially functional proteins. We present EvoGUD, a single-sequence–conditioned diffusion framework for large-step exploration of protein sequence space under learned evolutionary...
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Abstract:
Both natural and directed evolution are powerful in improving protein functions but they are slow in exploring the nearly endless sequence space. Here, we present SPIN-dvEvo that couples few-shot low-rank adaptation (LoRA) of an ESM-2 protein language model with a genetic algorithm to quickly evolve functional remote homologs from a local cluster of highly-homologous, binary-labeled sequences. We...
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Abstract:
Proteolysis Targeting Chimera (PROTACs) are a revolutionary drug modality that can expand the repertoire of druggable targets to proteins lacking conventional active sites or binding pockets1. However, the majority of PROTACs developed are against already drugged targets2 suggesting it is challenging to discover novel binders of undruggable targets. To overcome this, we developed a scalable,...