Ras recruits and activates effectors that transmit receptor-initiated signals. Monomeric Ras can bind Raf; however, Raf's activation requires dimerization, which can be facilitated by Ras dimerization. Previously, we showed that active K-Ras4B dimerizes in silico and in vitro through two major interfaces:(i) β-interface, mapped to Switch I and effector-binding regions,(ii) α-interface at the allosteric lobe. Here, we chose constitutively active K-Ras4B as our control and two double mutants (K101D and R102E; and R41E and K42D) in the α-and...
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Microbes, commensals, and pathogens, control the numerous functions in the host cells. They can alter host signaling and modulate immune surveillance by interacting with the host proteins. For shedding light on the contribution of microbes to health and disease, it is vital to discern how microbial proteins rewire host signaling and through which host proteins they do this. Host-Microbe Interaction PREDictor (HMI-PRED) is a user-friendly web server for structural prediction of protein-protein interactions (PPIs) between the host and a microbial...
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While many proteins act alone, the majority of them interact with others and form molecular complexes to undertake biological functions at both cellular and systems levels. Two proteins should have complementary shapes to physically connect to each other. As proteins are dynamic and changing their conformations, it is vital to track in which conformation a specific interaction can happen. Here, we present a step-by-step guide to embedding the protein alternative conformations in each protein–protein interaction in a...
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Glucocorticoid (GR) and mineralocorticoid receptors (MR) are believed to classically bind DNA as homodimers or MR-GR heterodimers to influence gene regulation in response to pulsatile basal or stress-evoked glucocorticoid secretion. Pulsed corticosterone presentation reveals MR and GR co-occupy DNA only at the peaks of glucocorticoid oscillations, allowing interaction. GR DNA occupancy was pulsatile, while MR DNA occupancy was prolonged through the inter-pulse interval. In mouse mammary 3617 cells MR-GR interacted in the...
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Androgen receptor (AR) signalling is essential in nearly all prostate cancers. Any alterations to AR-mediated transcription can have a profound effect on carcinogenesis and tumor growth. While mutations of the AR protein have been extensively studied, little is known about those somatic mutations that occur at the non-coding regions where AR binds DNA. Using clinical whole genome sequencing, we show that AR binding sites have a dramatically increased rate of mutations that is greater than any other transcription factor...
View details for https://www.nature.com/articles/s41467-020-14644-y