Cellular Function of a Biomolecular Condensate Is Determined by Its Ultrastructure.

Biomolecular condensates play key roles in the spatiotemporal regulation of cellular processes. Yet, the relationship between atomic features and condensate function remains poorly understood. We studied this relationship using the polar organizing protein Z (PopZ) as a model system, revealing how its material properties and cellular function depend on its ultrastructure.

Updated resources for exploring experimentally-determined PDB structures and Computed Structure Models at the RCSB Protein Data Bank.

The Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB, RCSB.org), the US Worldwide Protein Data Bank (wwPDB, wwPDB.org) data center for the global PDB archive, provides access to the PDB data via its RCSB.

Tuning Intermediate Band Solar Cell Efficiency: The Interplay of Electric Fields, Composition, Impurities, and Confinement.

In this study, we investigated the influence of structural parameters, including active region dimensions, electric field intensity, In-composition, impurity position, and potential profiles, on the energy levels, sub-gap transitions, and photovoltaic characteristics of a p-GaN/i-(In, Ga)N/GaN-n (p-QW-n) structure. The finite element method (FEM) has been used to solve numerically the Schrödinger equation. We found that particle and sub-gap energy levels are susceptible to well width, electric field, and impurity position.

Structure and inhibition mechanisms of essential transporter efflux protein A.

A broad chemical genetics screen in to identify inhibitors of established or previously untapped targets for therapeutic development yielded compounds (BRD-8000.3 and BRD-9327) that inhibit the essential efflux pump EfpA. To understand the mechanisms of inhibition by these compounds, we determined the structures of EfpA with inhibitors bound at 2.

Integrative spatiotemporal modeling of biomolecular processes: application to the assembly of the Nuclear Pore Complex.

Dynamic processes involving biomolecules are essential for the function of the cell. Here, we introduce an integrative method for computing models of these processes based on multiple heterogeneous sources of information, including time-resolved experimental data and physical models of dynamic processes. We first compute integrative structure models at fixed time points and then optimally select and connect these snapshots into a series of trajectories that optimize the likelihood of both the snapshots and transitions between them.

The molecular architecture of the nuclear basket.

The nuclear pore complex (NPC) is the sole mediator of nucleocytoplasmic transport. Despite great advances in understanding its conserved core architecture, the peripheral regions can exhibit considerable variation within and between species. One such structure is the cage-like nuclear basket.

Multiscale photocatalytic proximity labeling reveals cell surface neighbors on and between cells.

Proximity labeling proteomics (PLP) strategies are powerful approaches to yield snapshots of protein neighborhoods. Here, we describe a multiscale PLP method with adjustable resolution that uses a commercially available photocatalyst, Eosin Y, which upon visible light illumination activates different photo-probes with a range of labeling radii. We applied this platform to profile neighborhoods of the oncogenic epidermal growth factor receptor and orthogonally validated more than 20 neighbors using immunoassays and AlphaFold-Multimer prediction.

Inflammatory Bowel Diseases and the Efficacy of Probiotics as Functional Foods.

Adverse intestinal microbiome profiles described as a dysbiotic gut are a complicit etiological operative factor that can progress and maintain inflammatory sequelae in the intestines. The disruption of the gut microbiome that ensues with intestinal dysbiosis is, for example, posited by decreases in the alpha-diversity of the gut microbiome, which is characterized by significant reductions in the abundance of bacterial members from the and phyla. Proteobacteria have often been recognized as gut microbial signatures of disease.

Cell Maps for Artificial Intelligence: AI-Ready Maps of Human Cell Architecture from Disease-Relevant Cell Lines.

This article describes the Cell Maps for Artificial Intelligence (CM4AI) project and its goals, methods, standards, current datasets, software tools , status, and future directions. CM4AI is the in the U.S.

Illuminating the function of the orphan transporter, SLC22A10, in humans and other primates.

SLC22A10 is an orphan transporter with unknown substrates and function. The goal of this study is to elucidate its substrate specificity and functional characteristics. In contrast to orthologs from great apes, human SLC22A10, tagged with green fluorescent protein, is not expressed on the plasma membrane.

Nanobody repertoire generated against the spike protein of ancestral SARS-CoV-2 remains efficacious against the rapidly evolving virus.

To date, all major modes of monoclonal antibody therapy targeting SARS-CoV-2 have lost significant efficacy against the latest circulating variants. As SARS-CoV-2 omicron sublineages account for over 90% of COVID-19 infections, evasion of immune responses generated by vaccination or exposure to previous variants poses a significant challenge. A compelling new therapeutic strategy against SARS-CoV-2 is that of single-domain antibodies, termed nanobodies, which address certain limitations of monoclonal antibodies.

The Molecular Architecture of the Nuclear Basket.

The nuclear pore complex (NPC) is the sole mediator of nucleocytoplasmic transport. Despite great advances in understanding its conserved core architecture, the peripheral regions can exhibit considerable variation within and between species. One such structure is the cage-like nuclear basket.

IHMCIF: An Extension of the PDBx/mmCIF Data Standard for Integrative Structure Determination Methods.

IHMCIF (github.com/ihmwg/IHMCIF) is a data information framework that supports archiving and disseminating macromolecular structures determined by integrative or hybrid modeling (IHM), and making them Findable, Accessible, Interoperable, and Reusable (FAIR). IHMCIF is an extension of the Protein Data Bank Exchange/macromolecular Crystallographic Information Framework (PDBx/mmCIF) that serves as the framework for the Protein Data Bank (PDB) to archive experimentally determined atomic structures of biological macromolecules and their complexes with one another and small molecule ligands (e.

In situ structure of actin remodeling during glucose-stimulated insulin secretion using cryo-electron tomography.

Actin mediates insulin secretion in pancreatic β-cells through remodeling. Hampered by limited resolution, previous studies have offered an ambiguous depiction as depolymerization and repolymerization. We report the in situ structure of actin remodeling in INS-1E β-cells during glucose-stimulated insulin secretion at nanoscale resolution.

Integrative spatiotemporal map of nucleocytoplasmic transport.

The Nuclear Pore Complex (NPC) facilitates rapid and selective nucleocytoplasmic transport of molecules as large as ribosomal subunits and viral capsids. It is not clear how key emergent properties of this transport arise from the system components and their interactions. To address this question, we constructed an integrative coarse-grained Brownian dynamics model of transport through a single NPC, followed by coupling it with a kinetic model of Ran-dependent transport in an entire cell.

Structural basis of prostaglandin efflux by MRP4.

Multidrug resistance protein 4 (MRP4) is a broadly expressed ATP-binding cassette transporter that is unique among the MRP subfamily for transporting prostanoids, a group of signaling molecules derived from unsaturated fatty acids. To better understand the basis of the substrate selectivity of MRP4, we used cryogenic-electron microscopy to determine six structures of nanodisc-reconstituted MRP4 at various stages throughout its transport cycle. Substrate-bound structures of MRP4 in complex with PGE, PGE and the sulfonated-sterol DHEA-S reveal a common binding site that accommodates a diverse set of organic anions and suggest an allosteric mechanism for substrate-induced enhancement of MRP4 ATPase activity.

Tools for assembling the cell: Towards the era of cell structural bioinformatics.

Cells consist of large components, such as organelles, that recursively factor into smaller systems, such as condensates and protein complexes, forming a dynamic multi-scale structure of the cell. Recent technological innovations have paved the way for systematic interrogation of subcellular structures, yielding unprecedented insights into their roles and interactions. In this workshop, we discuss progress, challenges, and collaboration to marshal various computational approaches toward assembling an integrated structural map of the human cell.

Learning Cognitive Flexibility: Neural Substrates of Adapting Switch-Readiness to Time-varying Demands.

An individual's readiness to switch tasks (cognitive flexibility) varies over time, in part, as the result of reinforcement learning based on the statistical structure of the world around them. Consequently, the behavioral cost associated with task-switching is smaller in contexts where switching is frequent than where it is rare, but the underlying brain mechanisms of this adaptation in cognitive flexibility are not well understood. Here, we manipulated the likelihood of switches across blocks of trials in a classic cued task-switching paradigm while participants underwent fMRI.

A Clinicopathological Analysis of Molecular Subtypes of Breast Cancer using Immunohistochemical Surrogates: A 6-Year Institutional Experience from a Tertiary Cancer Center in North India.

Puneet Kaur Somal  Classification of breast cancer into different molecular subtypes has important prognostic and therapeutic implications. The immunohistochemistry surrogate classification has been advocated for this purpose. The primary objective of the present study was to assess the prevalence of the different molecular subtypes of invasive breast carcinoma and study the clinicopathological parameters in a tertiary care cancer center in rural North India.

Bibliographic dataset of literature for analysing global trends and progress of the machine learning paradigm in space weather research.

The field of space weather research has witnessed growing interest in the use of machine learning techniques. This could be attributed to the increasing accessibility of data, which has created a high demand for investigating scientific phenomena using data-driven methods. The dataset, which is based on bibliographic records from the Web of Science (WoS) and Scopus, was compiled over the last several decades and discusses multidisciplinary trends in this topic while revealing significant advances in current knowledge.

Multi-scale photocatalytic proximity labeling reveals cell surface neighbors on and between cells.

The cell membrane proteome is the primary biohub for cell communication, yet we are only beginning to understand the dynamic protein neighborhoods that form on the cell surface and between cells. Proximity labeling proteomics (PLP) strategies using chemically reactive probes are powerful approaches to yield snapshots of protein neighborhoods but are currently limited to one single resolution based on the probe labeling radius. Here, we describe a multi-scale PLP method with tunable resolution using a commercially available histological dye, Eosin Y, which upon visible light illumination, activates three different photo-probes with labeling radii ranging from ∼100 to 3000 Å.