Allosteric interactions are typically considered to proceed through a series of discrete changes in bonding interactions that alter the protein conformation. Here we show that allostery can be mediated exclusively by transmitted changes in protein motions. We have characterized the negatively cooperative binding of cAMP to the dimeric catabolite activator protein (CAP) at discrete conformational states. Binding of the first cAMP to one subunit of a CAP dimer has no effect on the conformation of the other subunit. The dynamics of the system, however, are modulated in a distinct way by the sequential ligand binding process, with the first cAMP partially enhancing and the second cAMP completely quenching protein motions. As a result, the second cAMP binding incurs a pronounced conformational entropic penalty that is entirely responsible for the observed cooperativity. The results provide strong support for the existence of purely dynamics-driven allostery.
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http://dx.doi.org/10.1038/nsmb1132 | DOI Listing |
Ann Rheum Dis
January 2025
Meinig School of Biomedical Engineering, Cornell University, Ithaca, New York, USA. Electronic address:
Objectives: This study aims to elucidate the microbial signatures associated with autoimmune diseases, particularly systemic lupus erythematosus (SLE) and inflammatory bowel disease (IBD), compared with colorectal cancer (CRC), to identify unique biomarkers and shared microbial mechanisms that could inform specific treatment protocols.
Methods: We analysed metagenomic datasets from patient cohorts with six autoimmune conditions-SLE, IBD, multiple sclerosis, myasthenia gravis, Graves' disease and ankylosing spondylitis-contrasting these with CRC metagenomes to delineate disease-specific microbial profiles. The study focused on identifying predictive biomarkers from species profiles and functional genes, integrating protein-protein interaction analyses to explore effector-like proteins and their targets in key signalling pathways.
Radiology
January 2025
From the Departments of Radiology (V.K., A.R., P.D.) and Pathology (J.N.), University of Arkansas for Medical Sciences, 4301 W Markham St, Little Rock, AR 72205.
A 61-year-old male patient without prior history of ophthalmologic problems presented with pain and redness in the left eye associated with slowly progressive proptosis over the previous 6 months. The patient also had diplopia in rightward and downward gaze. There was no vision loss.
View Article and Find Full Text PDFBMJ Case Rep
January 2025
Smt. Kanuri Santhamma Centre for Vitreo Retinal Diseases, Anant Bajaj Retina Institute, LV Prasad Eye Institute, Hyderabad, Telangana, India
A septuagenarian man presented with a visual acuity of hand motions and a large refractory macular hole (MH). We performed an autologous retinal transplant (ART) and covered the graft with fibrin glue without any endotamponade. The autograft was found to have dislocated from the MH when the patient was reviewed 1 week later.
View Article and Find Full Text PDFInt J Sports Physiol Perform
January 2025
Laboratory of the Metabolic Adaptations to Exercise Under Physiological and Pathological Conditions (AME2P) UPR 3533, CRNH Auvergne, Clermont Auvergne University, Clermont-Ferrand, France.
Purpose: The impact of weight cycling (WC)-successive weight loss (WL) and weight regain (WG)-on athlete performance is well documented, but effects on appetite are not. This study assessed the impact of a WC episode on dietary and appetitive profiles in athletes, considering sex and sport type.
Methods: Athletes (28 male, 20 female) from combat (n = 23), strength (n = 12), and endurance (n = 13) sports participated in 3 conditions during a WC episode (baseline, WL, WG).
PLoS One
January 2025
Institute of Medical Biochemistry, Center for Molecular Biology of Inflammation, University of Muenster, Muenster, Germany.
Weibel-Palade bodies (WPB) are secretory organelles exclusively found in endothelial cells and among other cargo proteins, contain the hemostatic von-Willebrand factor (VWF). Stimulation of endothelial cells results in exocytosis of WPB and release of their cargo into the vascular lumen, where VWF unfurls into long strings of up to 1000 µm and recruits platelets to sites of vascular injury, thereby mediating a crucial step in the hemostatic response. The function of VWF is strongly correlated to its structure; in order to fulfill its task in the vascular lumen, VWF has to undergo a complex packing/processing after translation into the ER.
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