J. Kuriyan

A Fluorescence-Based Sensor for Calibrated Measurement of Protein Kinase Stability in Live Cells

The paper develops a fluorescence-based sensor to measure protein kinase stability in live cells and shows its utility in studying oncogenic mutations and HSP90 chaperone effects.

Adaptive capacity of a DNA polymerase clamp-loader ATPase complex

The paper shows that single point mutations can restore function to a defective DNA polymerase clamp-loader complex by compensating for reduced affinity between the clamp loader and the sliding clamp.

Conditional Requirement for Dimerization of the Membrane-Binding Module of BTK

This study investigates whether BTK dimerization via its PH-TH module is required for signaling in B and T cells, finding it is not necessary in B cells but essential in T cells.

Crystal Structure of the kinase domain of a receptor tyrosine kinase from a choanoflagellate, Monosiga brevicollis

The paper determines the crystal structure of a receptor tyrosine kinase from Monosiga brevicollis and shows its ability to phosphorylate tyrosine residues.

Nanomolar inhibition of SARS-CoV-2 infection by an unmodified peptide targeting the pre-hairpin intermediate of the spike protein

Saturation mutagenesis of a predicted ancestral Syk-family kinase

The paper generates a bacterial-expressible Syk-family kinase via ancestral sequence reconstruction and uses deep mutational scanning to identify functional mutations.

A Saturation-Mutagenesis Analysis of the Interplay Between Stability and Activation in Ras

This study shows that cancer hotspot mutations in Ras activate it regardless of stability, while non-hotspot mutations can be activating or deleterious depending on stability.

A two-component protein condensate of EGFR and Grb2 regulates Ras activation at the membrane

This study shows that EGFR and Grb2 form a condensate that regulates Ras activation through phosphorylation and dimerization.

Differences in the dynamics of the tandem-SH2 modules of the Syk and ZAP-70 tyrosine kinases

This study compares the conformational dynamics of the tandem-SH2 modules in Syk and ZAP-70 kinases, revealing differences in their autoinhibited states and activation mechanisms.

Allosteric communication in DNA polymerase clamp loaders relies on a critical hydrogen-bonded junction

The paper identifies a hydrogen-bonded junction in DNA polymerase clamp loaders that is critical for allosteric communication, preserved across diverse AAA+ ATPases.

A molecular mechanism for the generation of ligand-dependent differential outputs by the epidermal growth factor receptor

This study identifies how EGFR differentiates signaling outputs from EGF and TGF- through conformational changes in its extracellular domain.

GHB confers neuroprotection by stabilizing the CaMKIIα hub domain

This study shows that GHB stabilizes the CaMKII hub domain, providing neuroprotection in cellular and mouse models.

CRISPR-Cas12a exploits R-loop asymmetry to form double strand breaks

This study shows that Cas12a uses R-loop asymmetry to cut the second DNA strand without direct protein interaction, explaining its double-strand break mechanism.

Flexible linkers in CaMKII control the balance between activating and inhibitory autophosphorylation

This study shows that differences in kinase-hub linker lengths between CaMKII and CaMKII-β isoforms affect their autophosphorylation balance, with CaMKII favoring activation and CaMKII-β favoring inhibition.

Variation in assembly stoichiometry in non-metazoan homologs of the hub domain of Ca2+/Calmodulin-dependent protein kinase II

The paper shows that hub domain assemblies of CaMKII-like proteins in green algae form larger oligomers than metazoan homologs, and that sequence changes can alter assembly stoichiometry.

Switch-like activation of Bruton’s tyrosine kinase by membrane-mediated dimerization

The paper identifies a switch-like PIP3 sensing mechanism in Btk's PH-TH module that enhances sensitivity through dimerization and multiple PIP3 binding.

Deep mutational analysis reveals functional trade-offs in the sequences of EGFR autophosphorylation sites

The paper uses mutational analysis to show how EGFR phosphosite sequences balance phosphorylation efficiency and adapter protein binding.

Fine-tuning of substrate preferences of the Src-family kinase Lck revealed through a high-throughput specificity screen

The paper develops a high-throughput method to map tyrosine kinase specificities and identifies differences in substrate recognition between Lck and c-Src.