QB3

Mechanisms of intracellular pH gating and local anesthetic inhibition of the two-pore domain K + channel TASK-2

TWIK-related acid-sensitive K+ channel 2 (TASK-2) is a pH sensing two-pore K + (K2P) channel that regulates respiration in brainstem neurons and systemic pH homeostasis in kidney. Despite its physiological importance and implication in disease, the molecular basis for intracellul...

Peptide-mediated CRISPR delivery: From dish to bloodstream

CRISPR-based therapeutics have advanced rapidly, but clinical translation remains bottlenecked by delivery. Standard carriers like viral vectors and lipid nanoparticles (LNPs) face challenges regarding cargo capacity, immunogenicity, and restricted tissue tropism. Peptide-mediate...

A noncontiguous code for RNA-guided DNA recognition at the origin of CRISPR-Cas

CRISPR-Cas provides RNA-mediated adaptive immunity, but how its first RNA-guided effector arose is unclear. In this study, we report the discovery of Viral Interference Programmable Repeat (VIPR) systems consisting of a Vipr protein ancestral to the earliest CRISPR-Cas effectors...

VIPR RNA-guided DNA recognition by noncontiguous geometric triplex formation

Viral interference programmable repeat (VIPR) systems use a noncontiguous code for RNA-guided transcriptional silencing. How the Vipr protein and a VIPR RNA (vrRNA) comprising alternating GGY and NN segments achieve precise DNA targeting is unknown. Here, we present 21 cryo–elect...

Reconstitution of multistep recruitment of ULK1 to membranes in autophagy

Abstract The Human ULK1 autophagy-initiating complex consists of ULK1, FIP200, and the HORMA domain heterodimer ATG13:ATG101. PI3P is essential to recruit ULK1C to membranes for ULK1, but ULK1C subunits do not contain PI3P-binding domains. Here we show that the ATG13:ATG101 dimer...

Prefoldin function links meiotic chromosome segregation with cellular remodeling and reveals tubulin sensitivity of the meiotic spindle

Abstract Faithful chromosome segregation is essential for producing viable gametes during meiosis, a specialized type of cell division compared to mitosis. Unlike mitosis, meiosis involves two consecutive chromosome segregation events without an intervening round of DNA replicati...

The immunophenotype and proviral landscape of HIV-infected CD4 T cells during antiretroviral therapy

In individuals on effective antiretroviral therapy, integrated HIV proviruses persist within CD4 T cells, forming a viral reservoir that rebounds if treatment is stopped. Identifying and targeting these rare, infected cells is critical for advancing therapies, but methods to stud...