Rules for connectivity of secondary structure elements in protein: Two–layer αβ sandwiches

Abstract

In protein structures, the fold is described according to the spatial arrangement of secondary structure elements (SSEs: α-helices and β-strands) and their connectivity. The connectivity or the pattern of links among SSEs is one of the most important factors for understanding the variety of protein folds. In this study, we introduced the connectivity strings that encode the connectivities by using the types, positions, and connections of SSEs, and computationally enumerated all the connectivities of two-layer αβ sandwiches. The calculated connectivities were compared with those in natural proteins determined using MICAN, a nonsequential structure comparison method. For 2α-4β, among 23,000 of all connectivities, only 48 were free from irregular connectivities such as loop crossing. Of these, only 20 were found in natural proteins and the superfamilies were biased toward certain types of connectivities. A similar disproportional distribution was confirmed for most of other spatial arrangements of SSEs in the two-layer αβ sandwiches. We found two connectivity rules that explain the bias well: the abundances of interlayer connecting loops that bridge SSEs in the distinct layers; and nonlocal β-strand pairs, two spatially adjacent β-strands located at discontinuous positions in the amino acid sequence. A two-dimensional plot of these two properties indicated that the two connectivity rules are not independent, which may be interpreted as a rule for the cooperativity of proteins.

Prediction of chaperonin GroE substrates using small structural patterns of proteins

“…Interestingly, all KDTs were derived from the common substructure between the TIM β/α barrel and the other α/β proteins. Note that 2α4β is ubiquitous and the most abundant substructure in the structural domains [ 34 , 45 , 46 , 47 ]. Targeting this structural pattern should be an effective strategy for GroE to maximize its assistance of numerous proteins.…”

The Structural Rule Distinguishing a Superfold: A Case Study of Ferredoxin Fold and the Reverse Ferredoxin Fold

“…Here, for further advancing the design technology, it is crucial to develop a systematic method to distinguish less designable structures and highly designable ones into each of which a large number of different sequences can fold [ 13 ]. Investigating the occurrence of structural folds among natural proteins provides a clue to this problem [ 14 , 15 , 16 , 17 , 18 ]. An ordinary fold appears in only one or a few superfamilies, but a particular fold is shared by a large number of superfamilies; such a particular fold was called a superfold [ 19 ].…”