Eight binding repeats

A particularly interesting VLDL receptor homolog is that of the chicken (termed LDL receptor relative with eight binding repeats, or LR8 Fig. 4), because its functions are documented by both biochemical and genetic evidence. LR8 mediates a key step in the reproductive effort of the hen, that is, oocyte growth via deposition of yolk lipoproteins... 

Bujo, H., Hermann, M., Kaderli, M.O., Jacobsen, L., Sugawara, S., Nimpf, J., Yamamoto, T., Schneider, W.J. 1994. Chicken oocyte growth is mediated by an eight ligand binding repeat member of the LDL receptor family. EMBO J. 13 5165-5175. 

The two homologous repeats, each of 88 amino acids, at both ends of the TBP DNA-binding domain form two stmcturally very similar motifs. The two motifs each comprise an antiparallel p sheet of five strands and two helices (Figure 9.4). These two motifs are joined together by a short loop to make a 10-stranded p sheet which forms a saddle-shaped molecule. The loops that connect p strands 2 and 3 of each motif can be visualized as the stirmps of this molecular saddle. The underside of the saddle forms a concave surface built up by the central eight strands of the p sheet (see Figure 9.4a). Side chains from this side of the P sheet, as well as residues from the stirrups, form the DNA-binding site. No a helices are involved in the interaction area, in contrast to the situation in most other eucaryotic transcription factors (see below). 

Fig. 12.5. Schematic summary of the eight T. canis proteins containing predicted SXC (NC6) domains. The consensus is shown in the N-terminal domain of PEB-1 (phosphatidylethanolamine-binding protein-1) as xCxDxxxDC(6x)C(11x) RCxxTCxxC. This consensus is faithfully repeated in MUC-1 (mucin-1), MUC-2, MUC-4 and MUC-5, and in all but the C-terminal domain of MUC-3. This domain (and the C-terminal SXC domain of PEB-1) show consensus spacing but some variation in consensus residues. Two additional proteins with quadrupled SXC domains differ in spacing between cysteines-2, -3 and -4, and show more variation in consensus residues. These are VAH-1 (venom allergen homologue) and HUF-001 (homologue of unknown function-001).

The N-terminal region of NgR harbors eight canonical leucine rich repeats (LRR) that contain the LRR-signature sequence LxxLxLN/CxL. The NgR LRRs are flanked by a leucine rich repeat N-terminal subdomain (LRRNT) and a leucine rich repeat C-terminal subdomain (LRRCT), which are small protein motifs frequently found next to LRR domains. Binding studies reveal that the leucine rich domains are necessary and sufficient for ligand recognition (Fournier et al., 2002). 

The inhibitor of apoptosis proteins (lAPs), which are characterized by the presence of one or more baculovirus lAP repeat (BIR) domains, are a family of endogenous apoptosis inhibitors that possess multiple antiapoptotic activities, including binding and inhibition of active caspases 3, 7, and 9. By inhibiting the downstream caspases 3 and 7, lAPs block the convergence point of multiple caspase activation pathways and thus inhibit apoptosis induced by various stimuli (81). At least eight human lAP members have been identified, of which XIAP (X-linked lAP) and survivin have received the most attention as therapeutic targets (82). 

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