Disulfide-bridged dimers

The neutral complex [Fe2(CO)6S2] (65) is known to undergo reduction to form the disulfide-bridged dimeric compound [Fe4S4(CO)i2]2- (66),60 which on further reduction yields [Fe2(CO)6S2]2 (67).61-62 The nucleophilic character of the bridging sulfides in the fully reduced dianion 67 is demonstrated by its reaction with a variety of metal halides to yield metal clusters in which the butterfly unit of 67 acts as a bidentate ligand coordinated via the bridging sulfides.63-66 With alkyl halides, 67 reacts to form S-alkylated products.60-63... 

Figure 8.9. Determination of contact sites. Cysteine residues were incorporated into the polypeptide chains of the monomers. In the corresponding oligomer, the cysteine residues ate oxidized. If the monomer s cysteine residues are situated near the contact sites of the monomers, the oxidation causes covalent cross-linking of the oligomer (disulfide bridges). Dimers, trimers, and so on appear in the SDS gel (nonreducing conditions).

Beer L, Reed RW, Robertson CM, Oakley RT, Tham FS, Haddon RC (2008) Tetrathio-phenalenyl radical and its disulfide-bridged dimer. Org Lett 10 3121-3123... 

The analogous reaction with sodium sulfide gives a dimeric product 4 that contains a disulfide bridge.212... 

Disulfide bridges formation ChEs contain 8-10 cysteines six of these form three internal disulfide bridges. The cysteine that is located four amino acids upstream the carboxyl terminus forms a disulfide bridge with a cysteine of an identical subunit, creating an interchain disulfide bridge, which stabilizes the dimeric structure. 

Figure 48-3. Schematic representation of fibronectin. Seven functional domains of fibronectin are represented two different types of domain for heparin, cell-binding, and fibrin are shown. The domains are composed of various combinations of three structural motifs (I, II, and III), not depicted in the figure. Also not shown is the fact that fibronectin is a dimer joined by disulfide bridges near the carboxyl terminals of the monomers. The approximate location of the RGD sequence of fibronectin, which interacts with a variety of fibronectin integrin receptors on cell surfaces, is indicated by the arrow. (Redrawn after Yamada KM Adhesive recognition sequences.

Fig. 1. Oligomerization of CXC chemokines. (A) Monomeric form of CXCL8 (IL-8) with disulfide bridges shown as black sticks. (B) Dimeric form of CXCL8 showing six-stranded P-sheet. (C) Tetrameric form of CXCL10 (IP-10).

Structural and functional evidence clearly demonstrates that family C receptors function as dimers, either as homodimers or as heterodimers. The metabotropic glutamate receptors and the calcium sensors, as discussed in Section 2.6.1, are found as covalently connected dimers in which there is a disulfide bridge between a Cys residue located in a loop in the N-terminal extracellular domain of each monomer. This disulfide bridge apparently serves only to hold the monomers in close proximity, as the loop is so unstructured that it does not resolve in the x-ray structure. 

Nilsson, M., Wang, X., Rodziewicz-Motowidlo, S., Janowski, R., Lindstrom, V., Onnerfjord, P., Westermark, G., Grzonka, Z., Jaskolski, M., and Grubb, A. (2004). Prevention of domain swapping inhibits dimerization and amyloid fibril formation of cystatin C Use of engineered disulfide bridges, antibodies, and carboxymethylpapain to stabilize the monomeric form of cystatin C.J. Biol. Chem. 279, 24236- 24245. 

In an enzymic reaction catalysed by glutathione peroxidase, GSH reacts with peroxides and becomes oxidized to form a dimer (GSSG) linked by a disulfide bridge. 

Fia. 2. Fractionation of human serum high-density lipoprotein ap>oprotein (apo HDD, scheme 2. Such a procedure takes advantage of the dimer— monomer conversion of fraction IV induced by the cleavage of the single disulfide bridge. R-IV = reduced fraction IV 8ME — 3-meroaptoethanol. Peaks — fraction HI = fraction IV fraction V. 

Contrary to early belief (S32), it is now established that, in its native form, fraction IV represents a dimer having its two identical or nearly identical monomers linked together by a single disulfide bridge (B5, S17, S19). The complete amino acid sequence of this polypeptide has recently been published (B5) and is represented in Fig. 4. Each monomer has been... 

Frazao, C., Sieker, L., Sheldrick, G. M., Famzin, V.,LeGall,J. and Carrondo, M. A. (1999). Ab initio structure solution of a dimeric cytochrome c3 from Desulfovibrio gigas containing disulfide bridges. /. Biol. Inorg. Chem. 4, 162-165. 

Since hemoproteins such as lactoperoxidase and catalase are inhibited more rapidly than the sulfhydryl oxidation occurs, it is unlikely that the rapid activation of guanylate cyclase occurs by sulfhydryl oxidation [132]. Prolonged incubation of the papain or dehydrogenase enzymes with substrate and nitroprusside yielded a turbidity which indicated denaturation of the enzyme to an insoluble form, possibly by the formation of disulfide bridges via the dimerization of thiyl radicals [132]. 

Cleavage of the Trt group of one chain 54 with a weak acid to give 55 and its subsequent thiolysis of the. S -SPy derivative of the second chain 57 directs the formation of the first interchain disulfide bond in 58. The second interchain disulfide bridge is formed between the two Acm-protected cysteine residues of the [bis(Acm), bis(tBu), mono-disulfide]-hetero-dimer 58 by treatment with iodine. Finally, treatment of 59 with chlorosilane/sulfoxide produces the third disulfide bond between the two tBu-protected cysteine residues yielding human insulin (42). 

Oxidation of mono-cysteine peptides to the dimer is a straightforward reaction that can produce only the desired product. In the case of bis-cysteine peptides statistically the oxidation leads to the homodimers in parallel and antiparallel orientation as well as to the disulfide-bridged monomer and oligomers. When the two cysteine residues are placed in the adjacent position formation of homodimers is highly favored over the cyclic monomer (Section 6.1.5.1) and the product distribution depends strongly on the peptide concentration. Such a type of intermolecular disulfide bridging is present in bovine seminal ribonuclease, where an antiparallel alignment occurs at the interface of the dimer. 97 ... 

Among the methods established in cysteine chemistry for cleavage of the Mob group with concomitant formation of disulfide bridges, i.e. I2, Tl( III )trifluoroacetate140 and DMSO/ TFA,[411 only the DMSO/TFA procedure allows for clean deprotection of SeC(Mob) residues and for their concomitant oxidation to selenocystine dimers or intrachain cyclic structures. IP°33]... 

The mechanism of regulation of HRI kinase by heme is not well understood. Inactive and active forms of the HRI kinase differ in the content of intermolecular disulfide bridges of the HRI kinase dimer. However it is still imclear how heme targets the kinase and whether the disulfide bridges directly influence the kinase activity. 

Fig. 5.2. Structural principles of transmembrane receptors, a) Representation of the most important functional domains of transmembrane receptors, b) Examples of subunit structures. Transmembrane receptors can exist in a monomeric form (1), dimeric form (2) and as higher oligomers (3,4). Further subunits may associate at the extracellular and cytosohc domains, via disulfide bridges (3) or via non-covalent interactions (4). c) Examples of structures of the transmembrane domains of receptors. The transmembrane domain may be composed of an a-hehx (1) or several a-helices linked by loops at the cytosolic and extracellular side (2). The 7-helix transmembrane receptors are a frequently occurring receptor type (see 5.3). Several subunits of a transmembrane protein may associate into an ohgomeric structure (3), as is the case for voltage-controUed ion channels (e.g., K channel) or for receptors with intrinsic ion channel function (see Chapter 17).

In some cases, the ligand itself has a dimeric structure and induces formation of active receptor dimers on binding to the receptor. One example is PDGF, which exists as a disulfide bridge-linked dimeric protein. 

Figure 7-17 The structure of insulin. (A) The amino acid sequence of the A and B chains linked by disulfide bridges. (B) Sketch showing the backbone structure of the insulin molecule as revealed by X-ray analysis. The A and B chains have been labeled. Positions and orientations of aromatic side chains are also shown. (C) View of the paired N-terminal ends of the B chains in the insulin dimer. View is approximately down the pseudo-twofold axis toward the center of the hexamer. (D) Schematic drawing showing packing of six insulin molecules in the zinc-stabilized hexamer.

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