Robo receptors participate in the orchestration of several developmental responses, most notably axonal guidance in the central nervous system. Robo1 contains five tandem Ig-like and three fibronectin type-III (FnIII) domains in its ectodomain, followed by a single-pass transmembrane segment and an intracellular region. A human Robo1 construct that includes the two extracellular membrane-proximal fibronectin (Fn) domains and the juxtamembrane linker was overexpressed in Escherichia coli and purified. Crystals were obtained using the vapour-diffusion method at 293 K and X-ray diffraction data were collected. Molecular-replacement attempts using related Fn domains as search models did not result in a solution. After introducing two additional methionine residues using PCR site-directed mutagenesis, selenomethionine-derivative crystals were produced. These crystals belonged to the primitive orthorhombic space group P212121, with unit-cell parameters a = 27.24, b = 77.64, c = 91.91 Å. Assuming the presence of a monomer in the asymmetric unit gave a crystal volume per protein weight (VM) of 1.97 Å(3) Da(-1) and a solvent content of 37.6%. Anisotropic diffraction data and a fragmented single-wavelength anomalous dispersion electron-density map, to which homology-modelled domains were docked, were obtained.
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http://dx.doi.org/10.1107/S1744309113014863 | DOI Listing |
Sci Rep
December 2024
Department of Medical Biophysics, University of Toronto, Toronto, Canada.
Globally, prostate cancer is the second most common malignancy in males, with over 400 thousand men dying from the disease each year. A common treatment modality for localized prostate cancer is radiotherapy. However, up to half of high-risk patients can relapse with radiorecurrent prostate cancer, the aggressive clinical progression of which remains severely understudied.
View Article and Find Full Text PDFPhytomedicine
November 2024
School of Pharmacy, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, PR China; Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, PR China; Tongde Hospital, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310007, PR China; School of Pharmacy, Hangzhou Medical College, Hangzhou, Zhejiang 310007, PR China. Electronic address:
Sci Transl Med
November 2024
Cardiovascular Research Center, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06510, USA.
Roundabout (ROBO) 1 and 2 are transmembrane receptors that bind secreted SLIT ligands through their extracellular domains (ECDs) and signal through their cytoplasmic domains to modulate the cytoskeleton and regulate cell migration, adhesion, and proliferation. SLIT-ROBO signaling regulates pathological ocular neovascularization, which is a major cause of vision loss worldwide, but pharmacological tools to prevent SLIT-ROBO signaling are lacking. Here, we developed human monoclonal antibodies (mAbs) against the ROBO1 and ROBO2 ECDs.
View Article and Find Full Text PDFJ Mol Neurosci
November 2024
Department of Child and Adolescent Psychiatry, Faculty of Medicine, Sivas Cumhuriyet University, Sivas, Turkey.
Specific learning disorder (SLD) is prevalent worldwide and is a complex disorder with variable symptoms and significant differences among individuals. Epigenetic markers may alter susceptibility to neurodevelopmental disorders (NDDs). Aberrant expression of protein-coding (mRNA) genes in this pathology shows that the detection of epigenetic molecular biomarkers is of increasing importance in the diagnosis and treatment of individuals with SLD.
View Article and Find Full Text PDFImmunopharmacol Immunotoxicol
December 2024
Orthopedics Department, Ningxia Medical University General Hospital, Yinchuan, Ningxia, China.
Background: The aberrant H-type vessel formation was found to be intimately linked to subchondral bone remodeling during osteoarthritis (OA) development. Herein, we investigated the role and mechanism of osteoblast-secreted slit guidance ligand 3 (Slit3) in H-type vessel formation during OA progression.
Methods: Slit3 protein levels in subchondral bone samples of OA patients were detected.
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