Protein disulphide bridge

M Vasquez. Modeling side-chain conformation. Curr Opm Stiaict Biol 6 217-221, 1996. JM Thornton. Disulphide bridges m globular proteins. J Mol Biol 151 261-287, 1981. 

A small number of proteins, and again insulin is an example, are synthesized as pro-proteins with an additional amino acid sequence which dictates the final three-dimensional structure. In the case of proinsulin, proteolytic attack cleaves out a stretch of 35 amino acids in the middle of the molecule to generate insulin. The peptide that is removed is known as the C chain. The other chains, A and B, remain crosslinked and thus locked in a stable tertiary stiucture by the disulphide bridges formed when the molecule originally folded as proinsulin. Bacteria have no mechanism for specifically cutting out the folding sequences from pro-hormones and the way of solving this problem is described in a later section. 

By far the most studied family of the G-protein-coupled receptors are the rhodopsin-like receptors. These are also the largest group of receptors in number as they include receptors not only for the monoamines, nucleotides, neuropeptides and peptide hormones, but they also include the odorant receptors which number several hundreds of related receptors. These receptors have short N-termini, a conserved disulphide bridge between the TM2-TM3 and TM4—TM5 extracellular domains, and variable-length C-termini. In some cases the C-terminus is myristolyated which by tying the C-terminus to the cell membrane generates a fourth intracellular loop. 

Figure 1. A two-dimensional representation that illustrates the tracing of the interaction lines to give the peak-pass-peak-pass chain representative of the protein backbone, side chains and disulphide bridge. Circles represent passes and squares peaks. 

Figure 2. Correspondence of the calculated backbone trace with that of the reported backbone for BP2 [19], As well, the calculated disulphide bridges are included to illustrate the important role they play in protein structure, binding certain regions together. 

TNF- a was first purified from conditioned medium from HL-60 cells. It has a relative molecular mass of 17 kDa when analysed by SDS-PAGE, but 45 kDa when analysed by gel filtration. Thus, the molecule exists as a non-glycosylated trimer with a pi of 5.3. Each monomer comprises 157 amino acids and contains two cysteine residues that form a disulphide bridge. Trimer formation appears to be due to noncovalent interactions between the monomers. Human TNF-a is synthesised as a 233-amino-acid protein that is proteolytically cleaved during processing. Whilst the 17-kDa form is readily secreted (and hence can function as an extracellular mediator), a 26-kDa transmembrane form has also been identified. This form of TNF-a may thus function in cytotoxicity resulting from cell-cell contact. 

Unlike polysaccharides, proteins do not have branched chains, but several chains may be linked together via disulphide bridges rather than peptide bonds. The primary structure of ox insulin is shown in Fig. S.A2. The protein consists of two peptide chains which are linked via the formation of the disulphide bridges. Disulphide bridges are formed by the condensation of the thiol groups of two cysteine residues. 

In vivo, formation of the disulphide bridges in cyclotides might be facilitated by a protein disulphide isomerase (PDI) recently isolated from O. affinis,129 whereas backbone cyclisation is mediated by an asparaginyl endopepti-dase.130,131 Support for the latter proposal comes from the fact that a C-terminal Asn residue is essential for cyclisation of the peptide backbone. Violacin... 

A variety of aspartic protease inhibitor (API) proteins have been resolved from plants [122-135] of which the best characterized at the gene and protein level are those from Solanum tuberosum (potato) (Solanaceae) [124-134] (Table 4). The potato aspartic protease inhibitor proteins are typically about 190 residues (about 20 kDa), have 3 disulphide bridges, are homologous to the soybean trypsin inhibitor (Kunitz) family Pis [133] and can also inhibit trypsin [124-134] (Table 4). 

Ricin toxin consists of two protein moieties connected by a disulphide bridge. Chain A (Mw 32 kD) blocks the ribosomal activity, and chain B (Mw 34 kD) is responsible for cell entry of the A chain. 

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