The architecture of EGFR's basal complexes reveals autoinhibition mechanisms in dimers and oligomers

Our current understanding of epidermal growth factor receptor (EGFR) autoinhibition is based on X-ray structural data of monomer and dimer receptor fragments and does not explain how mutations achieve ligand-independent phosphorylation. Using a repertoire of imaging technologies and simulations we reveal an extracellular head-to-head interaction through which ligand-free receptor polymer chains of various lengths assemble. The architecture of the head-to-head interaction prevents kinase-mediated dimerisation. The latter, afforded by mutation or intracellular treatments, splits the autoinhibited head-to-head polymers to form stalk-to-stalk flexible non-extended dimers structurally coupled across the plasma membrane to active asymmetric tyrosine kinase dimers, and extended dimers coupled to inactive symmetric kinase dimers. Contrary to the previously proposed main autoinhibitory function of the inactive symmetric kinase dimer, our data suggest that only dysregulated species bear populations of symmetric and asymmetric kinase dimers that coexist in equilibrium at the plasma membrane under the modulation of the C-terminal domain

Perfil dos desvios posturais da coluna vertebral em adolescentes de escolas públicas do município de Juazeiro do Norte - CE

Postura é definida como sendo a posição adotada pelo ser humano. Dados epidemiológicos apontam para uma alta prevalência de alterações posturais de coluna entre crianças e adolescentes. O objetivo do presente estudo foi investigar os desvios posturais da coluna vertebral em escolares (n=670) de 11 a 19 anos. Utilizou-se como metodologia um simetrógrafo e uma máquina fotográfica para pesquisar a presença de desvios na coluna vertebral. Foram utilizados um nível d'água e uma régua para aferir a gibosidade, um fio de prumo e uma régua para medir os desvios laterais da coluna. Dos resultados obtidos, encontrou-se uma prevalência de 8,8% de desvios laterais e 2,4% de gibosidade, além de ser observada a presença de escoliose em portadores de assimetrias de ombros e ilíacos. Porém, não houve influência do peso, altura e índice de massa corporal (IMC) para a prevalência de escoliose. Dessa maneira, com este estudo, constatou-se elevada prevalência dos desvios posturais em escolares.Posture is defined as the position taken by humans. Epidemiological data indicate a high prevalence of backbone postural changes among children and adolescents. The aim of this study was to investigate the postural deviations of the spine in schoolchildren (n=670) from 11 to 19 years. The methodology used was a simetrograf and a camera for the presence of deviations in the spine. We used a water level and a ruler to measure the spinal deformity, a plumb line and a ruler to measure the lateral deviation of the spine. Of the obtained results it was found a prevalence of 8.8% of lateral deviation and 2.4% of gibbosity, besides it was observed the presence of scoliosis in patients with asymmetries in the shoulders and hipbones. However, there was no influence of weight, height and body mass index (BMI) for the prevalence of scoliosis. Thus, through this study, it was stated the high prevalence of postural deviations in schoolchildren