Abo1 ATPase facilitates the dissociation of FACT from chromatin.

The histone chaperone FAcilitates Chromatin Transcription (FACT) is a heterodimeric complex consisting of Spt16 and Pob3, crucial for preserving nucleosome integrity during transcription and DNA replication. Loss of FACT leads to cryptic transcription and heterochromatin defects. FACT was shown to interact with Abo1, an AAA + family histone chaperone involved in nucleosome dynamics.

Sarm1-Dependent Metabolic Reprogramming of Schwann Cells Following Nerve Injury.

Schwann cells (SCs) transition into a repair phenotype after peripheral nerve injury, which is crucial for supporting axon regeneration. However, the early SC injury response preceding the repair state remains poorly understood. Here, we demonstrate that Sarm1, a key regulator of axon degeneration, is expressed in SCs and has a critical role in the early SC injury response.

Structure of the human ATAD2 AAA+ histone chaperone reveals mechanism of regulation and inter-subunit communication.

ATAD2 is a non-canonical ATP-dependent histone chaperone and a major cancer target. Despite widespread efforts to design drugs targeting the ATAD2 bromodomain, little is known about the overall structural organization and regulation of ATAD2. Here, we present the 3.

Single-Molecule Imaging Reveals the Mechanism Underlying Histone Loading of AAA+ ATPase Abo1.

Chromatin dynamics is essential for maintaining genomic integrity and regulating gene expression. Conserved bromodomain-containing AAA+ ATPases play important roles in nucleosome organization as histone chaperones. Recently, the high-resolution cryo-electron microscopy structures of Abo1 revealed that it forms a hexameric ring and undergoes a conformational change upon ATP hydrolysis.

Cryo-EM structure of Vibrio cholerae aldehyde-alcohol dehydrogenase spirosomes.

Aldehyde-alcohol dehydrogenase (AdhE) is a metabolic enzyme and virulence factor in bacteria. E. coli AdhE (eAdhE) multimerizes into spirosomes that are essential for enzymatic activity.

Structural basis of nucleosome assembly by the Abo1 AAA+ ATPase histone chaperone.

The fundamental unit of chromatin, the nucleosome, is an intricate structure that requires histone chaperones for assembly. ATAD2 AAA+ ATPases are a family of histone chaperones that regulate nucleosome density and chromatin dynamics. Here, we demonstrate that the fission yeast ATAD2 homolog, Abo1, deposits histone H3-H4 onto DNA in an ATP-hydrolysis-dependent manner by in vitro reconstitution and single-tethered DNA curtain assays.

Effects of hypertrophic and dilated cardiomyopathy mutations on power output by human β-cardiac myosin.

Hypertrophic cardiomyopathy is the most frequently occurring inherited cardiovascular disease, with a prevalence of more than one in 500 individuals worldwide. Genetically acquired dilated cardiomyopathy is a related disease that is less prevalent. Both are caused by mutations in the genes encoding the fundamental force-generating protein machinery of the cardiac muscle sarcomere, including human β-cardiac myosin, the motor protein that powers ventricular contraction.

Cytoplasmic dynein regulates its attachment to microtubules via nucleotide state-switched mechanosensing at multiple AAA domains.

Cytoplasmic dynein is a homodimeric microtubule (MT) motor protein responsible for most MT minus-end-directed motility. Dynein contains four AAA+ ATPases (AAA: ATPase associated with various cellular activities) per motor domain (AAA1-4). The main site of ATP hydrolysis, AAA1, is the only site considered by most dynein motility models.

The mechanism of dynein motility: insight from crystal structures of the motor domain.

Dynein is a large cytoskeletal motor protein that belongs to the AAA+ (ATPases associated with diverse cellular activities) superfamily. While dynein has had a rich history of cellular research, its molecular mechanism of motility remains poorly understood. Here we describe recent X-ray crystallographic studies that reveal the architecture of dynein's catalytic ring, mechanical linker element, and microtubule binding domain.

Crystal structure of the dynein motor domain.

Dyneins are microtubule-based motor proteins that power ciliary beating, transport intracellular cargos, and help to construct the mitotic spindle. Evolved from ring-shaped hexameric AAA-family adenosine triphosphatases (ATPases), dynein's large size and complexity have posed challenges for understanding its structure and mechanism. Here, we present a 6 angstrom crystal structure of a functional dimer of two ~300-kilodalton motor domains of yeast cytoplasmic dynein.

Structure and functional role of dynein's microtubule-binding domain.

Dynein motors move various cargos along microtubules within the cytoplasm and power the beating of cilia and flagella. An unusual feature of dynein is that its microtubule-binding domain (MTBD) is separated from its ring-shaped AAA+ adenosine triphosphatase (ATPase) domain by a 15-nanometer coiled-coil stalk. We report the crystal structure of the mouse cytoplasmic dynein MTBD and a portion of the coiled coil, which supports a mechanism by which the ATPase domain and MTBD may communicate through a shift in the heptad registry of the coiled coil.

Regulatory ATPase sites of cytoplasmic dynein affect processivity and force generation.

The heavy chain of cytoplasmic dynein contains four nucleotide-binding domains referred to as AAA1-AAA4, with the first domain (AAA1) being the main ATP hydrolytic site. Although previous studies have proposed regulatory roles for AAA3 and AAA4, the role of ATP hydrolysis at these sites remains elusive. Here, we have analyzed the single molecule motility properties of yeast cytoplasmic dynein mutants bearing mutations that prevent ATP hydrolysis at AAA3 or AAA4.