Abstract
The OB-fold is a diverse structure superfamily based on a β-barrel motif that is often supplemented with additional non-conserved secondary structures. Previous deletion mutagenesis and NMR hydrogen exchange studies of three OB-fold proteins showed that the structural stabilities of sites within the conserved β-barrels were larger than sites in non-conserved segments. In this work we examined a database of 80 representative domain structures currently classified as OB-folds, to establish the basis of this effect. Residue-specific values were obtained for the number of Cα-Cα distance contacts, sequence hydrophobicities, crystallographic B-factors, and theoretical B-factors calculated from a Gaussian Network Model. All four parameters point to a larger average flexibility for the non-conserved structures compared to the conserved β-barrels. The theoretical B-factors and contact densities show the highest sensitivity. Our results suggest a model of protein structure evolution in which novel structural features develop at the periphery of conserved motifs. Core residues are more resistant to structural changes during evolution since their substitution would disrupt a larger number of interactions. Similar factors are likely to account for the differences in stability to unfolding between conserved and non-conserved structures.
Highlights
The three-dimensional structures of proteins underlie their functions
We looked at 80 representatives of the 95 domain structures classified as OB-folds in the September 2007 version of the SCOP database [3,21], after excluding 16 domains that either had poor quality structures or a doubtful assignment to the OBfold
We found that on average the conserved -barrels have more hydrophobic sequences, larger numbers of contacts per residue, and smaller experimental and predicted B-factors compared to the non-conserved secondary structures
Summary
The three-dimensional structures of proteins underlie their functions. In spite of the growing number of structures available, the processes by which proteins fold remain poorly understood. Many proteins fold in a cooperative two-state transition, other proteins are less cooperatively organized, making it possible to characterize partially folded intermediate states. These partially folded states may offer the best chance to understand proteinfolding mechanisms [1,6,9,10,11,12]. As the number of protein structures with OB-fold motifs has grown, the superfamily has come to include proteins with considerably different functions; including metal-binding, protease inhibition, and chemotaxis. The OB-fold motif (Figure 1) consists of a 5-stranded anti-parallel Greek Key -barrel, formed by a -meander (strands 1 to 3) and a -hairpin (strands 4 and 5). Strand 1 has a conserved -bulge that allows anti-parallel connections of its
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