Disulfide-linked homodimers

BMP2 (650) 20pl2 BDA2, BMP2A Acts as a disulfide-linked homodimer and induces bone and cartilage formation... 

Grigorian, A., Bustamante, J., Hernandez, P.,et /. (2005) Extraordinarily stable disulfide-linked homodimer of human growth hormone. Protein... 

Two types of 15-kD subunits are present, one type beginning with N-terminal Ala and the other with N-terminal Leu. Pairs of these small 15-kD subunits are linked by covalent disulfide bonds that are broken only by the mercaptoethanol. The disulfide-linked subunits comprise the 30-kD species. (There is insufficient information to discern whether the 30-kD species consists of two different homodimers in which identical subunits are linked by disulfide bonds, or a unique heterodimer in which one Ala-initiated subunit is linked precisely to one Leu-initiated subunit.) Finally, two of the 30-kD species associate noncovalently to form the 60-kD particle that contains two copies each of two different 15-kD subunits. The 60-kD particle constitutes the native protein that is observed by molecular exclusion chromatography. (Urea disrupts the noncovalent subunit association, without breaking the disulfide bonds.)... 

For the synthesis of heterodimeric cystine peptides where two different peptide chains are cross-linked by a disulfide bridge random co-oxidation of the two chains besides producing the heterodimer leads in the optimal case to the additional two homodimers in statistical distribution. Therefore, chemical control of the disulfide bridging via site-directed disulfide formation techniques is required since a thermodynamic control for generation of heterodimers is extremely difficult to achieve (see Section 6.1.5). 

Scheme 1. Reduction of homodimer peptide linked via a disulfide bridge with dithio-threitol (DTT) and alkylation of the resulting thiol groups of both cysteines with either acrylamide (upper reaction) or iodoacetamide (lower reaction).

BCRP is classified in ABCG subfamily other members of this subfamily are involved in sterol transport (269). Unlike P-gp and MRPs, BCRP consists of a single ABC cassette in the amino terminal followed by six putative transmembrane domains however, it forms a homodimer linked by a disulfide bond in the plasma membrane (270,271). Initially, ABCG2 was identified as an mRNA expressed in placenta (272) and as a non-MDRl- and non-MRP-type resistance factor from cell lines selected in the presence of anthracy-clines and mitoxantrone (273). BCRP is expressed widely in the normal tissues (274) and localized on the canalicular membrane of the hepatocytes and apical membranes of epithelial cells (274,275) and brain capillary endothelial cells (276,277). 

In some cases, it is desirable to have a pharmaceutical protein in an aggregated state because it is the bioactive form of the protein. An example of this is surfactant protein B (SP-B), a pulmonary surfactant protein necessary for normal lung function in neonatal infants. " The protein exists exclusively as a homodimer in which the monomers are linked by a disulfide bond. In studies investigating efficacy of the SP-B monomer compared with the dimer in transgenic mice, it was found that although the surfactant action was preserved in the monomeric form of the protein, altered lung hysteresis was noted. The authors concluded that SP-B dimerization is required for optimal lung function. 

Becaplermin is produced by a recombinant strain of S. cerevisiae containing the gene for the B chain of PDGF. The protein has a molecular mass of approximately 2S kDa and is a homodimer composed of two identical polypeptide chains that are linked by disulfide bonds. It is a growth factor that activates cell proliferation, differentiation, and function, and it is rclea.sed from cells involved in the healing process. 

Glutathione reductase (EC 1.8.1.7 formerly EC 1.6.4.2 GSR) links the glutathione pathway to the hexose monophosphate pathway through the reversible oxidation and reduction of NADP. Flavin adenine dinucleotide (FAD) is necessary as a cofactor. The enzyme maintains high levels of reduced glutathione in the cell. Two isoforms exist, a mitochondrial and cytoplasmic form, produced by alternative initiation. The molecule is a homodimer, linked by a disulfide bridge. Each subunit (522 amino acids 56kDa) is divided into four domains of which domains one and two bind FAD and NADPH, respectively and domain four forms the interface. ... 

Figure 6.1-1. The x-ray crystal structure of a human insulin homodimer (A/B/C/D) at 1.5-A resolution (PDB ID IZEH). Each component of the dimer is composed of a smaller chain (A/C of 21 residues) linked by disulfide bridges to a larger chain (B/D of 30 residues).

Homodimer needs to be correctly assembled and linked via a disulfide-bond. 

PTTH is the abbreviation for "prothoracicotropic hormone". It is a homodimer linked by disulfide bridges. The monomer sequence is given. 

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