RESUMO
The Gag proteins of retroviruses play an essential role in virus particle assembly by forming a protein shell or capsid and thus generating the virion compartment. A variety of human proteins have now been identified with structural similarity to one or more of the major Gag domains. These human proteins are thought to have been evolved or "domesticated" from ancient integrations due to retroviral infections or retrotransposons. Here, we report that X-ray crystal structures of stably folded domains of MOAP1 (modulator of apoptosis 1) and PEG10 (paternally expressed gene 10) are highly similar to the C-terminal capsid (CA) domains of cognate Gag proteins. The structures confirm classification of MOAP1 and PEG10 as domesticated Gags, and suggest that these proteins may have preserved some of the key interactions that facilitated assembly of their ancestral Gags into capsids.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal , Proteínas Reguladoras de Apoptose , Proteínas de Ligação a DNA , Produtos do Gene gag , Proteínas de Ligação a RNA , Retroelementos/genética , Proteínas Adaptadoras de Transdução de Sinal/química , Proteínas Adaptadoras de Transdução de Sinal/genética , Sequência de Aminoácidos/genética , Proteínas Reguladoras de Apoptose/química , Proteínas Reguladoras de Apoptose/genética , Proteínas do Capsídeo/química , Proteínas do Capsídeo/genética , Sequência Conservada/genética , Proteínas de Ligação a DNA/química , Proteínas de Ligação a DNA/genética , Produtos do Gene gag/química , Produtos do Gene gag/genética , Humanos , Modelos Moleculares , Domínios Proteicos/genética , Proteínas de Ligação a RNA/química , Proteínas de Ligação a RNA/genética , Retroviridae/genética , Infecções por RetroviridaeRESUMO
INTRODUCTION: Healthrelated quality of life in patients with chronic obstructive pulmonary disease (COPD) can be measured by the Clinical COPD Questionnaire (CCQ). In this study, the CCQ was used to assess the therapeutic success of a fixeddose tiotropium / olodaterol combination treatment in Polish COPD patients. OBJECTIVES: We aimed to evaluate the changes in the CCQ score in Polish patients with COPD after 6 weeks of treatment with tiotropium / olodaterol and to assess the predictors of response to this treatment. PATIENTS AND METHODS: Data of the Polish subgroup of the NISCCQ observational study (NCT03663569) were extracted. COPD patients who had received a new tiotropium / olodaterol prescription were included. The primary end point was therapeutic success predefined as a 0.4point reduction in the CCQ score after 6 weeks of tiotropium / olodaterol treatment. Posthoc logistic regression analysis was performed to identify the predictors of response to the treatment. RESULTS: After 6 weeks of treatment, 72.4% of patients achieved therapeutic success. The therapy was successful in 83.4% of treatmentnaïve patients, as compared with 62.6% and 73.3% of those previously treated with longacting muscarinic antagonists or longacting ß2 agonists in monotherapy and in combination with inhaled corticosteroids, respectively. Therapeutic success was achieved by at least 50% of patients regardless of the COPD severity and exacerbation history but it was more frequent in patients with more severe disease. The airflow limitation severity grades 2 to 4, modified Medical Research Council Dyspnea Scale classes 2 to 4, exacerbations within the last year before the study, and treatmentnaïve status predicted a better response to tiotropium / olodaterol. CONCLUSIONS: Tiotropium / olodaterol treatment improved clinical control in Polish COPD patients. Therapeutic success was the most pronounced in individuals with more severe COPD and in the treatmentnaïve group but occurred also in those with moderate disease and in previously treated participants.