Protein dimerization, mediation

An example for such an arrangement is the Met repressor of E. coli. The palindromic recognition sequence of the MeO repressor occurs in 2-5 copies on the DNA. The repressor itself binds as a dimer on one copy of the recognition sequence. Protein-protein interactions mediate cooperative binding of the repressor dimers to the adjacent copies of the recognition sequence. 

Structural analysis indicates that the fos and jun proteins belong to a class of DNA-binding proteins that share the conserved structural motif known as the leucine zipper (see fig. 31.21). Thus, the dimerization of these two proteins is mediated by hydrophobic interaction between the leucine side chains of two leucine zipper domains. 

FGF. An X-ray structure of a heparin-linked biologically active dimer of fibroblast growth factor was described (170). The fibroblast growth factors (FGFs) form a large family of structurally related, multifunctional proteins that mediate cellular functions by binding to transmembrane FGF receptors (171,172). 

The Ugand-occupied receptor dimer does not have inherent tyrosine kinase activity but, rather, provides docking sites for 2 molecules of JAK2, a cytoplasmic tyrosine kinase of the Janus kinase family. The juxtaposition of 2 JAK2 molecules leads to trani-phosphorylation and autoactivation of JAK2, with consequent tyrosine phosphorylation of cytoplasmic proteins that mediate downstream signahng events (Figure 55-2). 

Thyroid hormone binds to receptors in the nucleus that control the expression of genes responsible for many metabolic processes. The T3 receptor exists in two monomeric forms alpha and beta. When activated by T3, the a and (3 monomers combine to form ao, PP, or aP dimers. These Tj-activated dimers bind to DNA response elements and control the synthesis of RNA, which codes for specific proteins that mediate the actions of thyroid hormones. 

A second simulation carried out one year later [80] appeared to vindicate partly this idea, since the inclusion of 30 counterions reduced overall DNA bending to 19°. This simulation concerned the ER protein dimer interacting with the consensus dimer sequence ERE-ERE or with a mixed GRE-ERE site. The results indicated that binding specificity and stability are conferred by a network of both direct and water mediated protein-DNA hydrogen bonds. With the consensus sequence, this network involves three water molecules, the residues Glu 25, Lys 28, Lys 32 and Arg 33 and several DNA bases. In the nonconsensus sequence, a fluctuating network of hydrogen bonds allows water molecules to enter the protein-DNA interface and two additional waters are located at the interface. The authors also noted that the interaction of the protein with the DNA backbone is weaker with the consensus site than with the non-... 

Protein dimerization is most frequently mediated by HLH, leucine zipper, and ankyrin motifs. The ankyrin motif, which is present in a heterodimeric transcription factor, GGABP (for GGA-binding protein), consists of 33 amino acid repeats (62). 

Fig. 1. The GP Ib-IX-V complex. The complex consists of seven transmembrane polypeptides denoted GP Iba (mol wt 145,000), GP IbP (mol wt 24,000), GPIX (mol wt 17,000) and GP V (mol wt 82,000), in a stoichiometry of 2 2 2 1. The hatched region represents the plasma membrane. The area above the hatched region represents the extracellular space that below represents the cytoplasm. The complex is a major attachment site between the plasma membrane and the cytoskeleton. Two molecules associated with the cytoplasmic domain are depicted a 14-3-3 dimer, which may mediate intracellular signaling, and actin-binding protein, which connects the complex to the cortical cytoskeleton and fixes its position and influences its function.

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