Scaffold protein definition1/1/2024 ![]() This latter property can be identified from PPI databases if reliable data are available ( Figure 1b). The other common feature among known scaffolds is that they interact with at least two signalling proteins possessing some signalling related activity. Moreover, related scaffolds might contain similar domain signatures ( Table 2). Known scaffolds, however, often contain modular PPI domains (e.g. ![]() Therefore, their identification based on sequence is currently not possible. In contrast to enzymes and to other active signalling components, known classical scaffolds do not share common signature motifs. Naturally, classical biochemical characterization – the major method by which scaffolds have been identified in the past – will be still required to experimentally validate the role of scaffold candidates in cellular signalling. To assess the real importance and abundance of classical scaffold proteins, it would be important to devise methods that would be able to predict them. Interactome-based search and definition for classical scaffold proteins ![]() Because scaffolds possessing catalytic domains might operate differently from classical signalling scaffolds, this current review focuses on the classical group only.īox 1. Some proteins that are clearly considered scaffolds because they bind to multiple enzymatic partners also contain a catalytic domain, illustrating how it is possible for a protein to have both a catalytic and scaffolding function. Therefore, reliable PPI databases and sophisticated PPI discovery techniques will probably be instrumental to indentify scaffold candidates systematically in the future ( Box 1). Because scaffolds assemble signalling proteins into functional modules through various protein–protein interactions (PPIs), it might be possible to search for them based on their PPI interaction profiles. Ste5) – were discovered through systematic genetics screens on model organisms. ![]() Historically, many active signalling components with kinase, phosphatase, GTPase, ion channel, protease or secondary messenger synthesis or degradation activity – and even some scaffolds (e.g. Thus, scaffold proteins so far have been mainly discovered on an individual basis, after they had been shown to bind to a better known protein kinase or ion channel, or to other effector proteins ( Table 1). Unfortunately, the scaffold definition given here does not enable straightforward identification of novel scaffold proteins. Adaptors in the literature, however, are assigned to have amore limited role compared with scaffolds: they bind to only two other proteins and frequently direct these into specific cellular locations. Of note, the term adaptor protein is also widely used to describe proteins that are functionally similar to scaffolds. ![]() Classical scaffolds usually do not possess any type of enzymatic activity and they can be regarded as specificity elements that selectively facilitate signalling between their bound components. kinases or phosphatases), receptors or ion channels. They bind at least two signalling enzymes (e.g. Scaffold proteins are molecules that bind multiple signalling components and promote their communication or interaction with each other. (Ste5 binds all components of a three-tiered mitogen-activated protein kinase cascade from S accharomyces cerevisiae.) We now know that proteins similar to Ste5 are abundant. At that time, it was a novelty to discover a protein that binds several components of a signalling cascade simultaneously. Approximately 15 years ago, Ste5 became established as one of the first well-characterized scaffold proteins ( Figure 1). ![]()
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