Biotin-painted proteins have thermodynamic stability switched by kinetic folding routes.

Biotin-labeled proteins are widely used as tools to study protein-protein interactions and proximity in living cells. Proteomic methods broadly employ proximity-labeling technologies based on protein biotinylation in order to investigate the transient encounters of biomolecules in subcellular compartments. Biotinylation is a post-translation modification in which the biotin molecule is attached to lysine or tyrosine residues. So far, biotin-based technologies proved to be effective instruments as affinity and proximity tags. However, the influence of biotinylation on aspects such as folding, binding, mobility, thermodynamic stability, and kinetics needs to be investigated. Here, we selected two proteins [biotin carboxyl carrier protein (BCCP) and FKBP3] to test the influence of biotinylation on thermodynamic and kinetic properties. Apo (without biotin) and holo (biotinylated) protein structures were used separately to generate all-atom structure-based model simulations in a wide range of temperatures. Holo BCCP contains one biotinylation site, and FKBP3 was modeled with up to 23 biotinylated lysines. The two proteins had their estimated thermodynamic stability changed by altering their energy landscape. In all cases, after comparison between the apo and holo simulations, differences were observed on the free-energy profiles and folding routes. Energetic barriers were altered with the density of states clearly showing changes in the transition state. This study suggests that analysis of large-scale datasets of biotinylation-based proximity experiments might consider possible alterations in thermostability and folding mechanisms imposed by the attached biotins.

One year of COVID-19 pandemic: Epidemiological characteristics of COVID-19 in the city of Uberaba, Minas Gerais, Brazil / Um ano da pandemia de COVID-19: características epidemiológicas da COVID-19 na cidade de Uberaba, Minas Gerais, Brasil

Introduction: The new coronavirus pandemic (COVID-19) is unprecedented in recorded human history. It spread from Wuhan, China, in early December, 2019, crossing the entire planet and reaching Brazilian shores in the following February. It was declared a pandemic on March 11, 2020, with the first case  recorded in the city of Uberaba, state of Minas Gerais, Brazil, on March 18, 2020. Since then, we have been collecting data and assessing the evolution of this fatal disease. Objective: In this work, we report the epidemiological characteristics of one year of the COVID-19 in Uberaba, and discuss its implications to the general public. Method: This is an observational, descriptive, documentary and retrospective study to describe the epidemiological profile of COVID-19 cases in the city of Uberaba from March 18, 2020 to March 17, 2021. Results: The study shows that the young-working age population are those who most spread the virus; however, the elderly are those who suffer and die the most, with slight differences regarding sex. This is in line with the reported national and international epidemiological profiles that show a shifting tendency of younger generations to be increasingly active on the evolution of the pandemic. We observed two major peaks on the two epidemiological time-series, confirmed cases and deaths, with an average age of 41 years old for the confirmed cases and 68 for the confirmed deaths. It was also reported that the lethality rate was 2.45%, and 80.00% of the confirmed deaths suffered from some previous health condition. Conclusions: In this sense, a permanent epidemiological surveillance has to take place in order to guide public health counter-measurements. The epidemiological characteristics of COVID-19 in Uberaba and related analyses are reported in the online observatory at https://coviduberaba.github.io.

Introdução: A pandemia do novo coronavírus (COVID-19) é inédita na história humana registrada. Espalhou-se de Wuhan, na China, no início de dezembro de 2019, cruzando todo o planeta e chegando à costa brasileira no mês de fevereiro seguinte. Foi declarada pandemia em 11 de março de 2020, com o primeiro caso registrado na cidade de Uberaba, estado de Minas Gerais, Brasil, em 18 de março de 2020. Desde então, estamos coletando dados e avaliando a evolução dessa fatalidade doença. Objetivo: Neste trabalho, relatamos as características epidemiológicas de um ano da COVID-19 em Uberaba e discutimos suas implicações para o público em geral. Método: Trata-se de um estudo observacional, descritivo, documental e retrospectivo para descrever o perfil epidemiológico dos casos de COVID-19 na cidade de Uberaba no período de 18 de março de 2020 até 17 de março de 2021. Resultados: O estudo mostra que a população jovem em idade ativa é a que mais espalha o vírus, no entanto, os idosos são os que mais sofrem e morrem, com pequenas diferenças em relação ao sexo. Isso está de acordo com os perfis epidemiológicos nacionais e internacionais relatados que mostram uma tendência de mudança das gerações mais jovens a serem cada vez mais ativas na evolução da pandemia. Observamos dois grandes picos nas duas séries temporais epidemiológicas, casos confirmados e óbitos, com média de idade de 41 anos para os casos confirmados e 68 para os óbitos confirmados. Também foi relatado que a taxa de letalidade foi de 2,45%, e 80,00% das mortes confirmadas sofriam de alguma condição de saúde anterior. Conclusões: Nesse sentido, uma vigilância epidemiológica permanente deve ocorrer para orientar as contramedidas de saúde pública. As características epidemiológicas da COVID-19 em Uberaba e análises relacionadas são relatadas no observatório online em https://coviduberaba.github.io.