B. T. Chait

Unique Binding and Stabilization Mechanisms Employed By and Engineered Into Nanobodies.

This study identifies mechanisms enabling nanobodies to bind antigens with high affinity and stability, revealing a conserved region critical for their function and suggesting strategies for their optimization.

Using a function-first "scout fragment"-based approach to develop allosteric covalent inhibitors of conformationally dynamic helicase mechanoenzymes

The paper develops covalent inhibitors for conformationally dynamic helicases using electrophilic scout fragments and a function-first approach, targeting SARS-CoV-2 nsp13 and human helicases BLM and WRN.

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

The paper shows that nanobodies against ancestral SARS-CoV-2 spike protein remain effective against recent variants, including omicron sublineages and emerging XBB/BQ.1.1 variants.

Differential dynamics specify MeCP2 function at methylated DNA and nucleosomes

This study investigates how MeCP2 interacts with methylated DNA and nucleosomes, revealing distinct dynamics that influence its function in gene repression and Rett syndrome.

Dynamic molecular mechanism of the nuclear pore complex permeability barrier

The paper investigates the dynamic behavior of the nuclear pore complex permeability barrier in yeast, showing it functions as a dynamic polymer brush rather than a phase-separated condensate.

Ultrasensitive detection of circulating LINE-1 ORF1p as a specific multi-cancer biomarker

This study develops ultrasensitive assays to detect ORF1p in plasma, showing its potential as a multi-cancer biomarker for early detection and monitoring.

Mex67 paralogs mediate division of labor in trypanosome RNA processing and export.

This study identifies distinct roles for three Mex67 paralogs in trypanosome RNA processing and export, showing non-redundant functions in mRNA export and ribosome biogenesis.

Structural basis for substrate selection by the SARS-CoV-2 replicase

This study uses cryo-EM to reveal how the SARS-CoV-2 RTC discriminates between natural NTPs and the antiviral remdesivir triphosphate, providing insights for antiviral design.

Shelterin is a Dimeric Complex with Extensive Structural Heterogeneity

This study characterizes the structural architecture and conformational variability of the human shelterin complex using multiple biophysical methods.

The MIDAS domain of AAA mechanoenzyme Mdn1 forms catch bonds with two different substrates

This study investigates how the MIDAS domain of Mdn1 forms catch bonds with two different UBL substrates under force, revealing force-dependent binding lifetime changes.

Nanobody Repertoires for Exposing Vulnerabilities of SARS-CoV-2

This paper presents a large repertoire of high-affinity nanobodies against SARS-CoV-2 Spike protein with potent neutralization properties and resistance to viral variants.

Structural basis for backtracking by the SARS-CoV-2 replication-transcription complex

This paper shows that SARS-CoV-2 RdRp undergoes backtracking, which may aid proofreading and antiviral resistance.

Biochemical reconstitutions reveal principles of human γ-TuRC assembly and function

This paper reconstitutes the human γ-TuRC and analyzes its structure and function, showing that the lumenal bridge is essential for microtubule nucleation.

Structural basis for transcription complex disruption by the Mfd translocase

The paper uses cryo-EM to visualize Mfd interacting with stalled RNA polymerase complexes, revealing its mechanism for initiating transcription-coupled repair.

Affinity proteomic dissection of the human nuclear cap-binding-complex interactome

This study maps the human nuclear cap-binding complex interactome using affinity proteomics to clarify the composition and interactions of NCBP1, NCBP2, and NCBP3-related macromolecular assemblies.

Asymmetric molecular architecture of the human γ-tubulin ring complex

This study presents a cryo-EM structure of the native human γ-tubulin ring complex, revealing its asymmetric architecture and identifying new structural features and interactions.

Interactions of nuclear transport factors and surface-conjugated FG nucleoporins: Insights and limitations

The paper evaluates three surface-based methods for characterizing protein-protein interactions involving intrinsically disordered proteins, revealing previously overlooked mass transport limitations and additional binding modes.

Modular assembly of the nucleolar large subunit processome

The paper determines cryo-EM structures of the nucleolar large subunit processome in different states, revealing how assembly factors prevent premature folding and enable distinct folding pathways.

The complete structure of the small subunit processome

The paper presents the cryo-EM structure of the yeast small subunit processome, revealing its atomic model and mechanisms preventing premature pseudoknot formation.