Two classes of riboswitches related to the guanidine-I riboswitch bind phosphoribosyl pyrophosphate (PRPP) and guanosine tetraphosphate (ppGpp). Here we report the co-crystal structure of the PRPP aptamer and its ligand. We also report the structure of the G96A point mutant that prefers ppGpp over PRPP with a dramatic 40,000-fold switch in specificity. The ends of the aptamer form a helix that is not present in the guanidine aptamer and is involved in the expression platform. In the mutant, the base of ppGpp replaces G96 in three-dimensional space. This disrupts the S-turn, which is a primary structural feature of the RNA motif. These dramatic differences in ligand specificity are achieved with minimal mutations. aptamers are therefore a prime example of an RNA fold with a rugged fitness landscape. The ease with which the aptamer acquires new specificity represents a striking case of evolvability in RNA.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6031431 | PMC |
| http://dx.doi.org/10.7554/eLife.36381 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Octadecaneuropeptide promotes the migration of astrocyte via ODN metabotropic receptor and calcium signaling pathway.
Peptides
January 2025
University of Tunis El Manar, Faculty of Sciences of Tunis, LR18ES03 Laboratory of Neurophysiology, Cellular Physiopathology and Biomolecules Valorisation. 2092 Tunis, Tunisia.
Migration is an essential characteristic of cells that occurs during many physiological and pathological processes. Astrocytes represent the most abundant cell type in the adult central nervous system (CNS), that play a crucial role in various functions such as guiding and supporting neuronal migration during development and maintaining brain homeostasis at adulthood. Astrocytes specifically synthesize and release endozepines, a family of regulatory peptides, including the octadecaneuropeptide (ODN).
View Article and Find Full Text PDFGenomic and molecular landscape of gallbladder cancer elucidating pathogenic mechanisms novel therapeutic targets and clinical implications.
Mutat Res
December 2024
School of Health Sciences and Technology, UPES, Dehradun, Uttarakhand 248007, India. Electronic address:
Gallbladder cancer (GBC) is an aggressive malignancy with a poor prognosis, often diagnosed at advanced stages due to subtle early symptoms. Recent studies have provided a comprehensive view of GBC's genetic and mutational landscape, uncovering crucial pathways involved in its pathogenesis. Environmental exposures, particularly to heavy metals, have been linked to elevated GBC risk.
View Article and Find Full Text PDFDual-Enzyme-Instructed Peptide Self-Assembly to Boost Immunogenic Cell Death by Coordinating Intracellular Calcium Overload and Chemotherapy.
ACS Nano
January 2025
Zhejiang Key Laboratory of Intelligent Cancer Biomarker Discovery and Translation, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou 325035, Zhejiang, P. R. China.
The concept of immunogenic cell death (ICD) induced by chemotherapy as a potential synergistic modality for cancer immunotherapy has been widely discussed. Unfortunately, most chemotherapeutic agents failed to dictate effective ICD responses due to their defects in inducing potent ICD signaling. Here, we report a dual-enzyme-instructed peptide self-assembly platform of (CPT-GFFpY-PLGVRK-Caps) that cooperatively utilizes camptothecin (CPT) and capsaicin (Caps) to promote ICD and engage systemic adaptive immunity for tumor rejection.
View Article and Find Full Text PDFNeurobiology of COVID-19-Associated Psychosis/Schizophrenia: Implication of Epidermal Growth Factor Receptor Signaling.
Neuropsychopharmacol Rep
March 2025
Molecular Psychoneuroimmunology, Institute for Genetic Medicine, Hokkaido University, Sapporo, Hokkaido, Japan.
COVID-19 exhibits not only respiratory symptoms but also neurological/psychiatric symptoms rarely including delirium/psychosis. Pathological studies on COVID-19 provide evidence that the cytokine storm, in particular (epidermal growth factor) EGF receptor (EGFR, ErbB1, Her1) activation, plays a central role in the progression of viral replication and lung fibrosis. Of note, SARS-CoV-2 virus (specifically, S1 spike domain) mimics EGF and directly transactivates EGFR, preceding the inflammatory process.
View Article and Find Full Text PDFPharmacological targeting of caspase-8/c-FLIP heterodimer enhances complex II assembly and elimination of pancreatic cancer cells.
Commun Biol
January 2025
Translational Inflammation Research, Medical Faculty, Otto von Guericke University (OvGU), Magdeburg, Magdeburg, Germany.
Extrinsic apoptotic network is driven by Death Ligand (DL)-mediated activation of procaspase-8. Recently, we have developed the first-in class small molecule, FLIPinB, which specifically targets the key regulator of extrinsic apoptosis, the protein c-FLIP, in the caspase-8/c-FLIP heterodimer. We have shown that FLIPinB enhances DL-induced caspase-8 activity and apoptosis.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!