RESUMO
[This corrects the article DOI: 10.1371/journal.pgen.1006321.].
RESUMO
The active sites of multisubunit RNA polymerases have a "trigger loop" (TL) that multitasks in substrate selection, catalysis, and translocation. To dissect the Saccharomyces cerevisiae RNA polymerase II TL at individual-residue resolution, we quantitatively phenotyped nearly all TL single variants en masse. Three mutant classes, revealed by phenotypes linked to transcription defects or various stresses, have distinct distributions among TL residues. We find that mutations disrupting an intra-TL hydrophobic pocket, proposed to provide a mechanism for substrate-triggered TL folding through destabilization of a catalytically inactive TL state, confer phenotypes consistent with pocket disruption and increased catalysis. Furthermore, allele-specific genetic interactions among TL and TL-proximal domain residues support the contribution of the funnel and bridge helices (BH) to TL dynamics. Our structural genetics approach incorporates structural and phenotypic data for high-resolution dissection of transcription mechanisms and their evolution, and is readily applicable to other essential yeast proteins.
Assuntos
Proteínas Mutantes/genética , RNA Polimerase II/genética , Saccharomyces cerevisiae/genética , Transcrição Gênica , Alelos , Catálise , Domínio Catalítico/genética , Cristalografia por Raios X , Proteínas Mutantes/química , Mutação , Dobramento de Proteína , Estrutura Secundária de Proteína , Transporte Proteico/genética , RNA Polimerase II/química , Saccharomyces cerevisiae/enzimologia , Especificidade por SubstratoRESUMO
CONTEXT: Exploring sports-related musculoskeletal injuries and treatment characteristics in middle school sports may help inform patient care decisions such as appropriate medical coverage. OBJECTIVE: To describe injury and treatment characteristics of middle school-aged athletes receiving care from athletic trainers within the Athletic Training Practice-Based Research Network (AT-PBRN). DESIGN: Descriptive study. SETTING: Middle school. PATIENT OR OTHER PARTICIPANTS: Middle school-aged athletes (n=1,011; male=503, female=506) with sports-related musculoskeletal injuries. MAIN OUTCOME MEASURE(S): Electronic patient records were analyzed from the AT-PBRN from 59 athletic trainers across 14 states between 2010-2022. Summary statistics (frequency, percentages, median, interquartile ranges [IQR]) were used to describe injury (age at injury, sex, sport, body part, diagnosis) and treatment characteristics (type of treatment, number of visits, number of procedures per visit). RESULTS: Football (17.7%, n=179), basketball (17.6%, n=178), and soccer (14.9%, n=151) reported the highest number of injuries. Ankle (17.2%, n=174), knee (16.5%, n=167), and head (14.1%, n=143) were the most common injury locations. Concussion (13.0%, n=131), ankle strain/sprain (12.4%, n=125), and thigh/hip/groin sprain/strain (11.1%, n=112) were the most reported diagnoses. Therapeutic exercise or activities (25.6%, n=1068), athletic trainer evaluation or re-evaluation (22.9%, n=957) and hot/cold packs (18.4%, n=766) were the most common services with a median of 2 visits (IQR=1-4) and 2 procedures (IQR=1-2) per visit. CONCLUSIONS: Football, basketball, and soccer reported the most musculoskeletal injuries for middle school-aged athletes. Concussions were the most frequent diagnosis, followed by ankle sprains/strains. Our findings are similar to prior investigations at high school and collegiate levels. Treatments at the middle school level were also similar to those that have been previously reported at the high school level with therapeutic exercise/activity, athletic trainer evaluation or re-evaluation, and hot/cold packs being the most common treatments. This information may be useful for informing patient care decisions at the middle-school level.