Transient interactions in metalloproteins




Transient protein complexes, with short lifetimes, are the result of compromise between the specificity and the instability of the binding. For metalloproteins, such features are even more pronounced because they are often engaged in electron transfer processes. Understanding the dynamics of the redox transient metallo-interactome and, in particular, of the interactions involving biomimetic interfaces requires a challenge based on specific proteomic tools.

Biological macromolecules are the key players of the cell factory, supporting and regulating cell metabolism and deciding on the life or death of the cell. The interactions between macromolecules take place on a wide range of timescales. Stable complexes, with lifetimes ranging from minutes to days, involve high-affinity and high-specificity binding, whereas transient complexes, with lifetimes in the second to microsecond range, are formed when fast turnover is required or reversible multicomponent assemblies must form. They, too, can exhibit high specificity. Such is the case for the interactions between proteins engaged in electron transfer and cell signalling.

A model for the formation of two-step complexes, mainly for those involving transient interactions, has recently been proposed. The first step yields the so-called encounter complex, and is dominated by electrostatics. During the encounter phase, the two partners remain largely solvated and adopt an ensemble of different orientations with a similar energy. Upon optimization of hydrophobic and electrostatic interactions between the desolvated partners, the transition towards the so-called productive complex occurs. Such a state is characterized by a well-defined orientation of the two partners within the complex, with the lowest energy value.

The three minireviews in this series report recent advances in our understanding of transient interactions between metalloproteins. They are all based on presentations at the Second Edition of the FEBS Workshop on Understanding Transient Molecular Interactions in Biology (Seville, 2010).

The first minireview – entitled Surface-enhanced vibrational spectroscopy for probing transient interactions of proteins with biomimetic interfaces: Electric field effects on structure, dynamics and function of cytochrome c – is focused on the influence of strong local electric fields on the structure and dynamics of metalloproteins after binding to biological membranes. To simulate the electric field effects, biomimetic interfaces are employed. The authors conclude that the electric fields may alter both the redox function of cytochrome c in the respiratory electron transport chain and its switch from redox to peroxidase activity, which is one of the key events in apoptosis.

In the second minireview – entitled Dynamics in electron transfer protein complexes – the role of the encounter state in molecular recognition between redox proteins is experimentally characterized by paramagnetic relaxation enhancement NMR and chemical shift perturbation. The electron transfer protein complexes are the result of a fine balance between the low-specificity encounter state and the high-specificity productive complex to meet the opposite requirements for rapid electron transfer and high turnover rate.

The third minireview – entitled Proteomic tools for the analysis of transient interactions between metalloproteins – summarizes the different techniques used for metallo-interactome analyses, as well as the most recent developments in metallomic tools, to provide a deeper insight into the underlying mechanisms of metal-related diseases. Metalloproteins, including electron transfer proteins, play major roles in cell metabolism and signalling pathways. Many of them are multitasking (moonlighting) proteins, for which the discovery of their partners may reveal novel functions. Although several methodological tools have recently been reported for the detection of protein interactions, specific approaches to studying the interactions involving metalloproteins are not well developed because they often form short-lived complexes that are difficult to detect.

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[ I. Díaz-Moreno is Assistant Professor of Biochemistry and Molecular Biology at the Institute of Plant Biochemistry and Photosynthesis, University of Seville – CSIC, Spain. She received a PhD degree in 2005 from the University of Seville, where she worked on molecular recognition between proteins and analysed the structures of their transient complexes. Later, she was an EMBO postdoctoral fellow until 2008 at the National Institute for Medical Research (NIMR-MRC) in London (UK), where she worked on the regulation mechanisms of mRNA decay by RNA-binding proteins. In 2010, she was awarded a permanent position at the University of Seville, where she researches transient protein complexes. ]

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[ M. Á. De la Rosa has been Full Professor of Biochemistry and Molecular Biology since 1995 at the Institute of Plant Biochemistry and Photosynthesis, University of Seville – CSIC, Spain. He is the director of the Scientific Research Centre Isla de la Cartuja, and President of the Spanish Society for Biochemistry and Molecular Biology. His research interests are mainly focused on the structure–function relationships of proteins, and on the transient complexes that they form. ]