3.6.2 The JAK–STAT pathway Another important protein kinase pathway is the JAK–STAT pathway. Cytokines (Section 2.2), are frequently used for signalling between cells of the immune system. Cytokine-induced signal transduction cascades are often direct pathways to the nucleus for switching on sets of genes. Janus kinases (JAKs, named after the two-faced Roman god) are a particular
3.4.2 Cyclic AMP The concentration of cyclic AMP (cAMP) in the cytosol increases 20-fold within seconds of an appropriate stimulus. This is achieved by the action of the plasma membrane-embedded protein adenylyl cyclase, which synthesizes cAMP from ATP (Figure 34). cAMP is short-lived, as with all second messengers, because it is continuously degraded by
3.1 Introduction We are now ready to describe in detail the major intracellular signalling pathways responsible for relaying the signal from the surface receptor to evoke a cellular response. This section will deal with signalling molecules that operate at the cytosolic leaflet of the plasma membrane (trimeric G proteins, monomeric G proteins and lipid-modifying enzymes), second messengers (such as Ca2+, cAMP, cGMP), protein kinases and phosphatases, and finally transcription factors.
1.8 Protein–protein interactions in signal transduction Many signalling proteins have both a catalytic domain and sometimes several binding domains.Some only have binding domains, enabling their proteins to act as adaptor, scaffold or anchoring proteins to bring other proteins together. Because of this multiplicity of binding domains, signalling proteins can potentially combine to form complexes with many other proteins; these complexes may be either transient (e.g. in response to stimulation by a growth factor), or stable (to target a protein to
1.6 Signalling proteins can act as molecular switches How does a signalling molecule actually convey a signal? With second messengers, it is easy to understand: they are produced or released in large quantities, diffuse to their target, to which they usually bind, bringing about a functional change, after which they are degraded or stored within a subcellular compartment (such as endoplasmic reticulum). With signalling proteins it is less obvious. Protein concentrations cannot fluctuate rapidly, and protein molecules cannot easily move within th
Introduction Even the simplest organisms can detect and respond to events in their ever-changing environment. Similarly, within a multicellular organism, cells are surrounded by an extracellular environment from which signals are received and responded to. Extracellular events are decoded and transmitted to relevant parts of individual cells by way of a series of activation/deactivation steps involving many intracellular molecules. This relay of information along molecular pathways is called signal tra
References 6.6 Summary of Section 6 The majority of proteins of known function are enzymes. Enzymes are biological catalysts, increasing the rates of reactions. Enzymes are not permanently altered by catalysis of a reaction. The transition state is an unstable intermediate enzyme–substrate complex in which the enzyme and the substrate are in highly strained conformations. There are a number of different catalytic mechanisms employed by enzymes including general 5.5 Summary of Section 5 Proteins are dynamic molecular machines. All proteins bind to other molecules, whether ions, small molecules or macromolecules, and these interactions are critical to the protein's function. The activity of proteins is regulated by changes in conformation. In allosterically regulated proteins, binding of one ligand affects the conformation of a remote part of the protein, thereby regulating interaction with a second ligand. Cooperative binding 5.3.2 Cooperative binding A feature of some proteins comprising more than one subunit is that binding of a ligand to its binding site on one subunit, can increase the affinity of a neighbouring subunit for the same ligand, and hence enhance binding. The ligand-binding event on the first subunit is communicated, via conformational change, to the neighbouring subunit. This type of allosteric regulation is called cooperative binding. Haemoglobin, as we have already discussed, is a tetramer consisting of two 5.2 All proteins bind other molecules All proteins bind to other molecules (generically termed ligands). Ligands that can bind to proteins include: ions, e.g. Ca2+; small molecules, e.g. H2O, O2 and CO2, glucose, ATP, GTP, NAD; macromolecules, i.e. proteins, lipids, polysaccharides, nucleic acids. These interactions are specific and key to the protein's function and, of course, are critically d 5.1 Introduction In some ways, proteins can be thought of as molecular machines, that through evolution have become highly specialised and efficient. Despite the somewhat static representations of proteins that you have met so far, proteins are in fact dynamic molecules. Not only are there internal movements, with conformational changes that are integral to protein function and regulation of function, but proteins, by virtue of their specific interactions with other cellular components, are essential to all t 3.4 The functional domains of Src To illustrate some of the principles of multidomain protein function, we will use as an example, the Src protein, a very well-characterised tyrosine kinase. As described earlier, Src contains four domains: two kinase domains, which together comprise the catalytic component of this protein, and two distinct binding/regulatory domains. The binding domains are of the SH2 and SH3 types. The identification of domains in other proteins, homologous to those in Src, led to the ‘Src ho 1.6 Fibrous proteins Most of the proteins described so far have been globular proteins. There are, however, some distinctive features that characterise fibrous proteins and we present here a general overview of these. Elongated fibrous proteins frequently play a structural role in the cell. They do not readily crystallise but tend to aggregate along their long axis to form fibres. X-ray diffraction studies of these fibres, in contrast to analysis of protein crystals, provides only very limited information on the 1.4.4 Covalent cross-linkages stabilise protein structure Proteins that are secreted by the cell, or are attached to the extracellular surface of the plasma membrane, can be subject to more extreme conditions than those experienced by intracellular proteins. Often, covalent cross-linkages stabilise these proteins by connecting specific amino acids within a polypeptide or between polypeptide chains in multisubunit proteins (see below). Typically such a linkage will be a covalent sulfur–sulfur bond which forms between the –SH groups of two cystein 1.4.2 Protein fold Protein folds are often very extensive arrangements, combining elements of secondary and supersecondary structure. Some of the most common protein folds are described in Table 4: view document with examples of proteins that contain them. Notice that proteins can be conveniently divided into three classes, on the basis of the elements of secondar 1.4.1 Motifs and supersecondary structures Supersecondary structures or motifs are particular arrangements and combinations of two or three secondary structures, often with defined topology (or connectivity). Table 3: view document describes some of the most common of these. The term ‘motif’ is also used to describe a consensus sequence of amino acids, i.e. a partial sequence c 1.1 Introduction Proteins are made up of one or more polypeptide chains, polymers of amino acid residues found in all proteins. The structure that a polypeptide adopts is determined by the component amino acid units – both their chemical properties and the order in which they occur in the polymer – and by the structure of the peptide bond that links them. Protein structure is described in terms of four levels of organisation: primary, secondary, tertiary and quaternary. The linear sequence of amino Introduction Proteins are the ‘doers’ of the cell. They are huge in number and variety and diverse in structure and function, serving as both the structural building blocks and the functional machinery of the cell. Just about every process in every cell requires specific proteins. Let us begin by listing some of the basic cellular processes and the role that proteins play. Chemical catalysis Enzymes, which are responsible for catalysing biological 1.3 Adding observations, images and locations to iSpot Observations are the main thing on the site. To make an observation, you need to provide this information: If you don't have a photograph just describe what you saw in as much detail as possible, including size, colour, behaviour etc. Y
