Homologous repeats

The horseshoe structure is formed by homologous repeats of leucine-rich motifs, each of which forms a p-loop-a unit. The units are linked together such that the p strands form an open curved p sheet, like a horseshoe, with the a helices on the outside of the p sheet and the inside exposed to solvent. The invariant leucine residues of these motifs form the major part of the hydrophobic region between the a helices and the p sheet. 

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). 

Davison, M., et al., 1989. Structural analysis of homologous repeated domains in ct-actinin and. spectrin. International Journal of Biological Macromolecules 11 81—90. 

Repeats in proteins can also be used to limit domain definitions. If a protein contains two homologous repeats, with a common motif separated by 200 amino acids, it can be inferred that the domain cannot be larger than 200 residues, although in this case the domain boundaries may not be known. 

Voltage-regulated sodium channels are the major participants in propagation of nerve impulses. Tire large 260-kDa a subunit of the sodium channel of nerve membranes contains four homologous repeat sequences, each of which may form transmembrane helices and also contain a loop that may participate in forming a pore similar to the K+ pore of Fig. 8-21.509 510a However, the structure is uncertain.511 Tire channel complex also contains 36- or 33-kDa Pj and P2 subunits that appear to be members of the Ig superfamily. 

DNA methylation also is present within tandem-repetitive DNA sequences in the heterochromatin. They also are thought to inhibit recombination between homologous repeats, which could lead to genomic instability (46). In fact, mutations of the DNMT3b cause centromeric instability. In addition, HDACs lie at the heart of heterochromatin pathways and can be recruited by transcriptional repressor or by methyl-DNA binding proteins. 

Fig. 3. Homologous repeat and homology of poly(ADP-ribose) synthetase (PARS) with c fos. One letter amino acid notation is used. Arrows show putative metal fingers for zinc as poly(ADP-ribose) synthetase is shown to be a zinc metallo enzyme (6).

MFS carriers are usually about 400 amino acyl residues (aa) long and have 12 transmembrane a-helical spanners (TMSs) with two homologous repeat units, each of six TMSs. They are found ubiquitously in bacteria, archaea, and eukaryotes. Over 20,000 sequenced MFS members are available for sequence analysis, and x-ray structures have been reported for several of them (Law et al. 2008). Some evidence suggests that the basic 6-TMS repeat unit arose by duplication of a primordial three TMS encoding genetic element and that MFS carriers arose from simple two TMS ion channels (Hvorup and Saier 2002 Vastermark et al. 2014). 

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