H-chains

Disulfides. As shown in Figure 4, the and h-chains of insulin are connected by two disulfide bridges and there is an intrachain cycHc disulfide link on the -chain (see Insulin and other antidiabetic drugs). Vasopressin [9034-50-8] and oxytocin [50-56-6] also contain disulfide links (48). Oxidation of thiols to disulfides and reduction of the latter back to thiols are quite common and important in biological systems, eg, cysteine to cystine or reduced Hpoic acid to oxidized Hpoic acid. Many enzymes depend on free SH groups for activation—deactivation reactions. The oxidation—reduction of glutathione (Glu-Cys-Gly) depends on the sulfhydryl group from cysteine. 

The reaction center is built up from four polypeptide chains, three of which are called L, M, and H because they were thought to have light, medium, and heavy molecular masses as deduced from their electrophoretic mobility on SDS-PAGE. Subsequent amino acid sequence determinations showed, however, that the H chain is in fact the smallest with 258 amino acids, followed by the L chain with 273 amino acids. The M chain is the largest polypeptide with 323 amino acids. This discrepancy between apparent relative masses and real molecular weights illustrates the uncertainty in deducing molecular masses of membrane-bound proteins from their mobility in electrophoretic gels. 

The most ingenious exocytosis toxins, however, come from the anaerobic bacteria Clostridium botulinum and Clostridium tetani. The former produces the seven botulinum neurotoxins (BoNTs) A-G the latter produces tetanus neurotoxin (TeNT). All eight toxins consist of a heavy (H) chain and a light (L) chain that are associated by an interchain S-S bond. The L-chains enter the cytosol of axon terminals. Importantly, BoNT L-chains mainly enter peripheral cholinergic terminals, whereas the TeNT L-chain mainly enters cerebral and spinal cord GABAergic and glycinergic terminals. The L-chains are the active domains of the toxins. They are zinc-endopeptidases and specifically split the three core proteins of exocytosis, i.e. the SNAREs (Fig. 1 inset). Each ofthe eight toxins splits a... 

Poly(dimethyl siloxanc) with vinyl or hydrosilanc (Si-H) chain ends have been converted to ATRP initiator ends e.g. Scheme 9.62) by hydrosilylalion, Bis-functional dimethyl siloxane polymers prepared in this way were used in polymerizations of S, MA, tsobornyl acrylate and BA to form ABA triblock copolymers. 

Five classes of H chain have been found in humans (Table 50-7), distinguished by differences in their Cjl regions. They are designated y, a, i 5, and e. The i and e chains each have four domains rather than the usual three. The type of H chain determines the class of immunoglobulin and thus its effector function. There are thus five immunoglobulin classes IgG, IgA, IgM, IgD, and IgE. The biologic functions of these five classes are summarized in Table 50-8. 

The L chains and H chains are synthesized as separate molecules and are subsequently assembled within the B cell or plasma cell into mature immunoglobulin molecules, all of which are glycoproteins. 

In a recent development, a new process of preparing borane-terminated isotactic polypropylene (z -PPs) via an in situ chain-transfer reaction was achieved by a styrene/hydrogen consecutive chain-transfer reagent, which avoids the use of a B—H containing chain-transfer agent.74 This has resulted in the utilization of milder polymerization conditions due to the use of the alkylaluminoxane cocatalyst (MAO) (50) (Fig. 33), which cannot normally be used in the presence of a B—H chain-transferring... 

Table 6.1 Amino-acid sequence alignment of four mammalian ferritins (Horse L chain, HoL Human L chain, HuL Human H chain, HuH Rat H, RaH) and of one of the ferritins, FTN, and the bacterioferritin, BFR of...

Figure 6.1 Schematic representation of human isoferritins of different subunit composition. Each ferritin subunit is represented as a sausage and subunits are packed in a symmetrical shell. Twelve of the 24 subunits are visible, with H-chain subunits stippled and L-chain subunits plain. Homopolymers of H-chain and L-chain subunits are at the top and bottom of the figure respectively. The sources of various ferritins are listed in the right hand column. Reprinted from Harrison and Arosio, 1996. Copyright (1996), with permission from Elsevier Science.

This is done a contre coeur, since the L-chain sequence was the first to be established. However, it makes little sense to refer to the amino terminus of H-chain ferritins as —1, —2, etc. 

The detailed high-resolution structure of the non-haem-containing ferritin of E. coli EcFTNA has been recently published (Stillman et al, 2000) and shows considerable structural similarity to human H-chain ferritin (r.m.s. deviation of main chain... 

Several binding sites for Tb3+ or Cd2+ ions have been identified in the interior of the apoferritin protein shell, some of which may be iron-binding sites (Harrison et ai, 1989 Granier et ah, 1998). In HoSF and HoLF, two sites were identified on the inner surface of the B helix at the subunit dimer interface (Figure 6.15, Plate 11) which bind two Cd2+ ions. One involves Glu-57 and Glu-60 as ligands and the other Glu-61 and Glu-64 (Granier et al., 1998). In H-chain ferritins the first pair of Glu-57 and Glu-60 are both replaced by His and only a single Tb3+ is found bound to Glu-61 and Glu-64 (Lawson et al, 1991). 

Inoue, S., Tanaka, K., Arisaka, F., Kimura, S., Ohtomo, K., and Mizuno, S. (2000a). Silk fibroin of Bombyx mori is secreted, assembling a high molecular mass elementary unit consisting of H-chain, L-chain, and P25, with a 6 6 1 molar ratio./. Biol. Chem. 275, 40517-40528. 

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