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The Asgard archaeal origins of Arf family GTPases involved in eukaryotic organelle dynamics.
Nat Microbiol
January 2025
Université Paris Cité, CNRS, Institut Jacques Monod, Paris, France.
The evolution of eukaryotes is a fundamental event in the history of life. The closest prokaryotic lineage to eukaryotes, the Asgardarchaeota, encode proteins previously found only in eukaryotes, providing insight into their archaeal ancestor. Eukaryotic cells are characterized by endomembrane organelles, and the Arf family GTPases regulate organelle dynamics by recruiting effector proteins to membranes upon activation.
View Article and Find Full Text PDFThe PH domain in the ArfGAP ASAP1 drives catalytic activation through an unprecedented allosteric mechanism.
bioRxiv
December 2024
Center for Structural Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD, USA.
ASAP1 is a multidomain Arf GTPase-activating protein (ArfGAP) that catalyzes GTP hydrolysis on the small GTPase Arf1 and is implicated in cancer progression. The PH domain of ASAP1 enhances its activity greater than 7 orders of magnitude but the underlying mechanisms remain poorly understood. Here, we combined Nuclear Magnetic Resonance (NMR), Molecular Dynamic (MD) simulations and mathematical modeling of functional data to build a comprehensive structural-mechanistic model of the complex of Arf1 and the ASAP1 PH domain on a membrane surface.
View Article and Find Full Text PDFSalmonella Typhimurium effector SseI regulates host peroxisomal dynamics to acquire lysosomal cholesterol.
EMBO Rep
December 2024
Pharmacology Division, CSIR-Central Drug Research Institute, Lucknow, India.
Salmonella enterica serotype Typhimurium (Salmonella) resides and multiplies intracellularly in cholesterol-rich compartments called Salmonella-containing vacuoles (SCVs) with actin-rich tubular extensions known as Salmonella-induced filaments (SIFs). SCV maturation depends on host-derived cholesterol, but the transport mechanism of low-density lipoprotein (LDL)-derived cholesterol to SCVs remains unclear. Here we find that peroxisomes are recruited to SCVs and function as pro-bacterial organelle.
View Article and Find Full Text PDFExploiting F NMR in a Multiplexed Assay for Small GTPase Activity.
J Am Chem Soc
January 2025
Department of Structural Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15260, United States.
Small GTPases (smG) are a 150-member family of proteins, comprising five subfamilies: Ras, Rho, Arf, Rab, and Ran-GTPases. These proteins function as molecular switches, toggling between two distinct nucleotide-bound states. Using traditional multidimensional heteronuclear NMR, even for single smGs, numerous experiments, high protein concentrations, expensive isotope labeling, and long analysis times are necessary.
View Article and Find Full Text PDFFunctional Divergence of the Closely Related Genes PhARF5 and PhARF19a in Flower Formation and Hormone Signaling.
Int J Mol Sci
November 2024
School of Landscape Architecture, Zhejiang Agriculture and Forestry University, Hangzhou 311300, China.
The ARF gene family plays a vital role in regulating multiple aspects of plant growth and development. However, detailed research on the role of the ARF family in regulating flower development in petunia and other plants remains limited. This study investigates the distinct roles of and in flower development.
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