Biophysical Reviews

Intrinsically disordered proteins (IDPs) are proteins that lack rigid 3D structure but exist as conformational ensembles. Because of their structural plasticity, they can interact with multiple partners. The protein interactions between IDPs and their partners form scale-free protein interaction networks (PINs) that facilitate information flow in the cell. Because of their plasticity, IDPs typically occupy hub positions in cellular PINs. Furthermore, their conformational dynamics and propensity for post-translational modifications contribute to “conformational” noise which is distinct from the well-recognized transcriptional noise. Therefore, upregulation of IDPs in response to a specific input, such as stress, contributes to increased noise and, hence, an increase in stochastic, “promiscuous” interactions. These interactions lead to activation of latent pathways or can induce “rewiring” of the PIN to yield an optimal output underscoring the critical role of IDPs in regulating information flow. We have used PAGE4, a highly intrinsically disordered stress-response protein as a paradigm. Employing a variety of experimental and computational techniques, we have elucidated the role of PAGE4 in phenotypic switching of prostate cancer cells at a systems level. These cumulative studies over the past decade provide a conceptual framework to better understand how IDP conformational dynamics and conformational noise might facilitate cellular decision-making.

Autoinhibition is an effective mechanism that guards proteins against spurious activation. Despite its ubiquity, the distinct organizations of the autoinhibited states and their release mechanisms differ. Signaling is most responsive to the cell environment only if a small shift in the equilibrium is required to switch the system from an inactive (occluded) to an active (exposed) state. Ras signaling follows this paradigm. This underscores the challenge in pharmacological intervention to exploit and enhance autoinhibited states. Here, we review autoinhibition and release mechanisms at the membrane focusing on three representative Ras effectors, Raf protein kinase, PI3Kα lipid kinase, and NORE1A (RASSF5) tumor suppressor, and point to the ramifications to drug discovery. We further touch on Ras upstream and downstream signaling, Ras activation, and the Ras superfamily in this light, altogether providing a broad outlook of the principles and complexities of autoinhibition.

Here is a brief summary of presentations made by the participants of the “Bioluminescence and Photonics of Fluorescent Proteins” session at the 9th Congress of the Russian Photobiological Society which were dedicated to basic studies on bioluminescence systems of different organisms as well as to various analytical applications of bioluminescent proteins. Many questions to the speakers and in-depth and comprehensive discussion of the results obtained demonstrated the researchers’ interest in this field of Photobiology.

This review covers the methods of computer simulation of protein interactions taking part in photosynthetic electron transport reactions. A direct multiparticle simulation method that simulates reactions describing interactions of ensembles of molecules in the heterogeneous interior of a cell is developed. In the models, protein molecules move according to the laws of Brownian dynamics, mutually orient themselves in the electrical field, and form complexes in the 3D scene. The method allows us to visualize the processes of molecule interactions and to calculate the rate constants for protein complex formation reactions in the solution and in the photosynthetic membrane. Three-dimensional multiparticle computer models for simulating the complex formation kinetics for plastocyanin with photosystem I and cytochrome bf complex, and ferredoxin with photosystem I and ferredoxin:NADP+-reductase are considered. Effects of ionic strength are featured for wild type and mutant proteins. The computer multiparticle models describe nonmonotonic dependences of complex formation rates on the ionic strength as the result of long-range electrostatic interactions.

This review is directed to researchers interested in a new point of view with relevance to nano-biomedicine. The first part covers the uses and potential of diacetylene lipid, 1,2-bis(10,12-tricosadiynoyl)-sn-glycero-3-phosphocholine (DC8,9PC) in facilitating biological target recognition. The second part concentrates on the use of albumin as a “soft” coating for nanoparticles. This review makes comment on how fabricated nanoparticles will assist with future human health applications.

Organoids are in vitro 3D self-organizing tissues that mimic embryogenesis. Organoid research is advancing at a tremendous pace, since it offers great opportunities for disease modeling, drug development and screening, personalized medicine, as well as understanding organogenesis. Mechanobiology of organoids is an unexplored area, which can shed light to several unexplained aspects of self-organization behavior in organogenesis. It is becoming evident that collective cell behavior is distinctly different from individual cells’ conduct against certain stimulants. Inherently consisting of higher number of degrees of freedom for cell motility and more complex cell-to-cell and cell-to-extracellular matrix behavior, understanding mechanotransduction in organoids is even more challenging compared with cell communities in 2D culture conditions. Yet, deciphering mechanobiology of organoids can help us understand effects of mechanical cues in health and disease, and translate findings of basic research toward clinical diagnosis and therapy.

Interferon regulatory factor 4 (IRF4) is a lymphoid transcription factor and a key regulator in the development of various immune cells, including T and B cells. It is well-known that IRF4 controls numerous decision-making processes relating to B cell development, including differentiation, maturation, and signalling. Consequently, genetic alterations that affect the functional aspects of IRF4 can result in clonal transformation and have been identified in various lymphoid malignancies. Over the last decades, a series of studies have demonstrated the critical cellular and structural basis underpinning IRF4-mediated B cell development and associated malignancies. In this review, we will briefly summarise the recent advances in understanding IRF4-mediated B cell development and related malignancies, with a particular focus on the molecular aspects that govern these processes.

Bayesian statistical learning provides a coherent probabilistic framework for modelling uncertainty in systems. This review describes the theoretical foundations underlying Bayesian statistics and outlines the computational frameworks for implementing Bayesian inference in practice. We then describe the use of Bayesian learning in single-cell biology for the analysis of high-dimensional, large data sets.