Beyond Consensus: Statistical Free Energies Reveal Hidden Interactions in the Design of a TPR Motif

Structure of Minimal Tetratricopeptide Repeat Domain Protein Tah1 Reveals Mechanism of Its Interaction with Pih1 and Hsp90

“…Helices 1B and 2A of Tah1 are closest in terms of primary sequence and length to the consensus helices found in TPR motifs, which are typically 14 residues long (40). Helix 1A of Tah1 consists of 16 residues and has an additional turn at the C terminus (Fig.…”

“…It is reasonable to suggest that this tight packing of helices contributes to the stability of Tah1. The majority of residues that are typically conserved in TPR domains and that are critical for stabilizing the hydrophobic core of these proteins are conserved in Tah1 (40). Hence, Tah1 can be considered to be a minimal TPR domain protein that can bind to Hsp90/Hsp70.…”

Consensus mutagenesis reveals that non-helical regions influence thermal stability of horseradish peroxidase

“…Thermal stability differences between homologous proteins may be due to a very few naturally occurring sequence variations ( [47] and references within). Magliery and Regan [48] have developed a more advanced model which addresses some of the inadequacies of the basic consensus approach [22]. The underlying principle of their improved consensus method defines the probability of occurrence of a particular residue at a specific position compared to a reference state; i.e.…”

“…it asks "how free is a position to vary, or change to another amino acid?" This method is potentially a very powerful test of covariance: the free energies of pairs of positions can be compared to determine if substitutions observed at one position in the sequence compensate for those observed at the other position [48]. In the present analysis, however, we wished merely to identify single positions that vary between peroxidase groups, as these positions are candidates for conferring stability.…”

Crystallization and preliminary X-ray crystallographic analysis of an artificial molten-globular-like triosephosphate isomerase protein of mixed phylogenetic origin

“…Because of the resource-intensive nature of library-based high-throughput methods, it is desirable to employ rational and semi-rational approaches for this purpose. With readily available sequence information, bioinformatics tools (Lockless & Ranganathan, 1999;Sü el et al, 2003;Magliery & Regan, 2004;Socolich et al, 2005;Russ et al, 2005) for elucidating various aspects of protein structure, function and activity are gaining popularity. It has been reported previously that making a consensus mutation, i.e.…”