The common structural and sequence features of the sandwich and barrel proteins. Application to the structural prediction and sequence classification

Alexander Kister
Rutgers University

We focus on the analysis of two large groups of the ß-proteins – sandwich-like and the barrel-like proteins. Each of these groups comprises about 70 different superfamilies and more than 40 protein folds according SCOP database classification. We showed that beta-proteins which grouped together on the basis of common architecture like sandwich-like or barrel-like proteins have commonality on the level of supersecondary structure. In both groups of ß-proteins – sandwich and barrel structures the arrangement of strands gives the invariants substructure – two "hydrophobic tetrahedrals". In the sandwich-like structure two "tetrahedrals" form so called "interlock". Residues of the interlock lie at the center of the interface between the beta sheets and form the common geometrical core of all sandwich proteins. In the barrel structures two tetrahedrals form another geometrical figure - "tetralock". Residues of the "tetralock" lie at the edge of two sub-sheets. The tetralock can be considered as the common geometrical core of the barrel proteins.
It was found that the key residues of the tetrahedrals form a pattern of the proteins, which can be considered as their sequence determinants. A direct corollary of our approach is that complexity of protein sequence search algorithms and 3D structure predictions can be dramatically reduced: instead of carrying out searches with whole protein sequences, we may now carry out searches with predefined sets of several key residues – patterns of the sandwich-like and the barrel-like proteins.

We show as well another advantage of the knowledge of the sequence determinants of the proteins. The analysis of the immunoglobulin molecules revealed the close correlation between the key residues and residues which involve in inter-domain interactions.

Parts of this work were carried out in collaboration with Drs. Vladimir Sobolev (Weizmann Institute, Israel), Alexei Finkelstein (Institute of Protein Research, Russia), Tanasis Fokas (University of Cambridge, UK), Michael Roytberg (Institute of Mathematical Problems of Biology, Russia) and Vladimir Potapov (Weizmann Institute, Israel)

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