Given the success of
Volume I of this Research Topic, and how rapid the subject area is evolving, we are pleased to announce the launch of Weak Interactions in Molecular Machinery Volume II.
Complex organization in both human societies and living cells relies on communication between their elements. Indeed, most cellular functions arise when communication is established through biomolecules that physically and specifically contact each other in a concerted manner to transmit messages efficiently.
The “molecular sociology” of the cells refers to all the interactions happening between macromolecules, with special emphasis on protein-protein, protein-nucleic acid, protein-carbohydrate, protein-membrane, and, in general, protein-ligand interactions. These tightly regulated events of binding occur on a wide range of timescales. Stable complexes, with lifetimes ranging from minutes to days, involve high affinity and high specificity binding. Amongst many others, these include irreversible enzyme inhibition and the assembly of proteins supporting the cell’s ultrastructure. Differently, transient interactions are characterized by a fine balance between specificity of binding and fast turnover rate, with the majority displaying equilibrium dissociation constants within the micromolar or even millimolar range. Perhaps counter-intuitively, these weaker molecular recognition mechanisms play key roles in most biological processes, including electron transfer chains in respiration and photosynthesis and the cell signalling cascades involving kinases and phosphatases.
Due to weak affinities and formation of short-lived states, transient complexes remain poorly understood despite their critical role in many biological events in living organisms. Over the last few years, several advancements in structural biology have offered unprecedented insight into transient molecular interactions. The growing number of NMR methods and pulse schemes to measure, for example, residual dipolar couplings (RDC) have expanded RDC applications, including structure determination and validation, determination of relative domain orientations, and the measurement of protein motions. Serial crystallography experiments using an X-ray free electron laser (XFEL), which allow to minimize radiation damage to crystals, have opened up opportunities to room temperature data collection, generating more biologically reliable data on structural dynamics in macromolecules. New generation of cameras with direct electron detection and increased frame rate, coupled with improved electron microscopes and new methods for sample preparation have massively expanded single-particle cryo-electron microscopy (cryo-EM) applicability, allowing to solve the structure of protein as small as ~26 kDa to near-atomic resolution. These methods have recently been complemented by high-throughput techniques to identify novel biomolecules that weakly bind to each other.
Such advances make the analysis of the transient biointeractome (the so-called trans-biointeractome) more affordable. Overall, trans-biointeractome analysis remains highly dependent on the specific technique employed. Therefore, the study of weakly interacting systems can be reliably tackled in depth only by adopting hybrid methods, which combine and integrate several biochemical and biophysical techniques.
This Research Topic aims to capture the state of the art of this broad field, focusing on the study of transient interactions, utilizing experimental or computational approaches. This work will provide an international platform for researchers to communicate the development of hybrid methods seeking to comprehensively understand cellular machines, their function and regulation.
