governs its interactions with host cells by secreting >300 different "effector" proteins. Some of these effectors contain eukaryotic domains such as the RCC1 (regulator of chromosome condensation 1) repeats promoting the activation of the small GTPase Ran. In this report, we reveal a conserved pattern of RCC1 repeat genes, which are distributed in two main clusters of strains. Accordingly, strain Philadelphia-1 contains two RCC1 genes implicated in bacterial virulence, ( eukaryotic gene 1), and , while strain Paris contains only one, The RCC1 repeat effectors localize to different cellular compartments and bind distinct components of the Ran GTPase cycle, including Ran modulators and the small GTPase itself, and yet they all promote the activation of Ran. The gene spans the corresponding open reading frames of and a separate adjacent upstream gene, and are fused upon addition of a single nucleotide to encode a protein that adopts the binding specificity of PieG. Thus, a point mutation in splits the gene, altering the effector target. These results indicate that divergent evolution of RCC1 repeat effectors defines the Ran GTPase cycle targets and that modulation of different components of the cycle might fine-tune Ran activation during infection. is a ubiquitous environmental bacterium which, upon inhalation, causes a life-threatening pneumonia termed Legionnaires' disease. The opportunistic pathogen grows in amoebae and macrophages by employing a "type IV" secretion system, which secretes more than 300 different "effector" proteins into the host cell, where they subvert pivotal processes. The function of many of these effector proteins is unknown, and their evolution has not been studied. RCC1 repeat effectors target the small GTPase Ran, a molecular switch implicated in different cellular processes such as nucleocytoplasmic transport and microtubule cytoskeleton dynamics. We provide evidence that one or more RCC1 repeat genes are distributed in two main clusters of strains and have divergently evolved to target different components of the Ran GTPase activation cycle at different subcellular sites. Thus, employs a sophisticated strategy to subvert host cell Ran GTPase during infection.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7157520 | PMC |
http://dx.doi.org/10.1128/mBio.00405-20 | DOI Listing |
PLoS Biol
April 2024
School of Medicine and Dentistry, University of Rochester, Rochester, New York, United States of America.
The densely packed centromeric heterochromatin at minor and major satellites is comprised of H3K9me2/3 histones, the heterochromatin protein HP1α, and histone variants. In the present study, we sought to determine the mechanisms by which condensed heterochromatin at major and minor satellites stabilized by the chromatin factor CFDP1 affects the activity of the small GTPase Ran as a requirement for spindle formation. CFDP1 colocalized with heterochromatin at major and minor satellites and was essential for the structural stability of centromeric heterochromatin.
View Article and Find Full Text PDFBiochemistry
April 2024
Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada.
Ras-related nuclear protein (Ran) is a member of the Ras superfamily of small guanosine triphosphatases (GTPases) and a regulator of multiple cellular processes. In healthy cells, the GTP-bound form of Ran is concentrated at chromatin, creating a Ran•GTP gradient that provides the driving force for nucleocytoplasmic transport, mitotic spindle assembly, and nuclear envelope formation. The Ran•GTP gradient is maintained by the regulator of chromatin condensation 1 (RCC1), a guanine nucleotide exchange factor that accelerates GDP/GTP exchange in Ran.
View Article and Find Full Text PDFJ Autoimmun
February 2023
KU Leuven, Department of Microbiology, Immunology and Transplantation, Clinical and Diagnostic Immunology, Leuven, Belgium; Laboratory Medicine, University Hospitals Leuven, Leuven, Belgium. Electronic address:
Purpose: In up to 20% of patients with systemic sclerosis (SSc) no known autoantibody specificity can be identified. Recently discovered autoantigens, such as telomeric repeat binding factor 1 (TERF1), as well as established autoantigens, like RuvBL1/2, are associated with telomere and telomerase biology. We aimed to identify new telomere- and telomerase-associated autoantigens in patients with SSc without known autoantibody specificity.
View Article and Find Full Text PDFBMC Plant Biol
August 2021
National Key Laboratory of Crop Genetic Improvement, College of Plant Science and Technology, Huazhong Agricultural University, Wuhan, 430070, China.
Background: Low temperature severely limits the growth, yield, and geographic distributions of soybean. Soybean plants respond to cold stress by reprogramming the expression of a series of cold-responsive genes. However, the intrinsic mechanism underlying cold-stress tolerance in soybean remains unclear.
View Article and Find Full Text PDFCase Rep Endocrinol
August 2020
Department of Urology, University of Florida College of Medicine-Jacksonville, Jacksonville, FL, USA.
Metastasis to the pituitary gland is extremely rare (∼2% of sellar masses). Clinical, biochemical, and radiologic characteristics of pituitary metastasis are poorly defined and can be difficult to diagnose before surgery. We present an unusual case with pituitary metastasis as the first manifestation of renal cell carcinoma (RCC).
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!