A helix-turn-strand structural motif common in alpha-beta proteins.

By exhaustive structural comparisons, we have found that about one-third of the alpha-helix-turn-beta-strand polypeptides in alpha-beta barrel domains share a common structural motif. The chief characteristics of this motif are that first, the geometry of the turn between the alpha-helix and the beta-strand is somewhat constrained, and second, the beta-strand contains a hydrophobic patch that fits into a hydrophobic pocket on the alpha-helix. The geometry of the turn does not seem to be a major determinant of the alpha-beta unit, because the turns vary in length from four to six residues. However, the motif does not occur when there are few constraints on the geometry of the turn-for instance, when the turns between the alpha-helix and the beta-strands are very long. It also occurs much less frequently in flat-sheet alpha-beta proteins, where the topology is much less regular and the amount of twist on the sheet varies considerably more than in the barrel proteins. The motif may be one of the basic building blocks from which alpha-beta barrels are constructed.     

A common channel-forming motif in evolutionarily distant porins.

Four new crystal packings of Escherichia coli porins are presented (phosphoporin, maltoporin, and two crystal forms of matrix porin). These were determined by molecular replacement methods using a polyalanine trial model acquired from the refined coordinates of porin from Rhodobacter capsulatus. The successful molecular replacement shows that the dominant motif found in R. capsulatus porin (a 16-stranded antiparallel beta-barrel) also applies to the E. coli porins, despite the lack of significant amino acid sequence homology. A 30 degrees-40 degrees tilt of the beta-strands with respect to the membrane normal was derived from the intensity distributions in the X-ray diffraction patterns for each porin studied, stressing their similarity. In view of the evolutionary distance between enteric and photosynthetic bacteria, the antiparallel beta-barrel may have significance as a basic structural motif for the formation of bacterial membrane channel structures.     

A novel common triplet profile for GC-rich prokaryotic genomes

It has been reported that there is a majority triplet profile among genomes, which was considered as a reflection of general mechanisms of genome evolution (Albrecht-Buehler, 2007). However, there are actually, according to our further analysis and at least among prokaryotic genomes, two common triplet profiles: one is from low-GC content genomes; the other is from high-GC content genomes. Both common profiles would be direct reflections of GC content variations and strand symmetry of genomic sequences.     

A common motif targets huntingtin and the androgen receptor to the proteasome

Huntington disease derives from a critically expanded polyglutamine tract in the huntingtin (Htt) protein; a similar polyglutamine expansion in the androgen receptor (AR) causes spinobulbar muscular atrophy. AR activity also plays an essential role in prostate cancer. Molecular mechanisms that regulate Htt and AR degradation are not well understood but could have important therapeutic implications. We find that a pentapeptide motif (FQKLL) within the Htt protein regulates its degradation and subcellular localization to cytoplasm puncta. Disruption of the motif by alanine substitution at the hydrophobic residues increases the steady state level of the protein. Pulsechase analyses indicate that the motif regulates degradation. A similar motif (FQNLF) has corresponding activities in the AR protein. Transfer of the Htt motif with five flanking amino acids on either side to YFP reduces the steady state YFP level by rendering it susceptible to proteasome degradation. This work defines a novel proteasome-targeting motif that is necessary and sufficient to regulate the degradation of two disease-associated proteins.