Structural trees for protein superfamilies

Abstract

Structural trees for large protein superfamilies, such as beta proteins with the aligned beta sheet packing, beta proteins with the orthogonal packing of alpha helices, two-layer and three-layer alpha/beta proteins, have been constructed. The structural motifs having unique overall folds and a unique handedness are taken as root structures of the trees. The larger protein structures of each superfamily are obtained by a stepwise addition of alpha helices and/or beta strands to the corresponding root motif, taking into account a restricted set of rules inferred from known principles of the protein structure. Among these rules, prohibition of crossing connections, attention to handedness and compactness, and a requirement for alpha helices to be packed in alpha-helical layers and beta strands in beta layers are the most important. Proteins and domains whose structures can be obtained by stepwise addition of alpha helices and/or beta strands to the same root motif can be grouped into one structural class or a superfamily. Proteins and domains found within branches of a structural tree can be grouped into subclasses or subfamilies. Levels of structural similarity between different proteins can easily be observed by visual inspection. Within one branch, protein structures having a higher position in the tree include the structures located lower. Proteins and domains of different branches have the structure located in the branching point as the common fold.

A global representation of the protein fold space

“…For example, there are Ͼ20 SCOP folds with similar ␤-sandwich architectures, of which a vast majority contain a common substructural unit at one end of the double layer (7)(8)(9). An interesting question is whether the fold space is continuous with respects to topological arrangement of the secondary structure elements such that structures exist for all possible topologies allowed for a polypeptide chain.…”

“…Such a bias is expected to impose a strong restriction on the shape of the fold space. On the other hand, even protein structures sharing common structural units such as the complete Greek key motif in ␤-sandwiches could show considerable structural diversity outside the common core (8,9), and the degree of variations is probably limited only by the size of the protein (or protein domain) and, ultimately, the number of different protein sequences in nature.…”

Origins and evolution of modern biochemistry: insights from genomes and molecular structure

“…A number of approaches have been used to characterize protein space and provide global views of the protein world directly from structure. This includes the generation of fold family trees (180,181), taxonomies based on secondary structure (182), metric distance comparison of structures (183), graph representations of domains based on scores of structural similarity (184,185), and a periodic table of structures (186), However, problems associated with the systematic classification of architectures at a topological level, make it difficult, if not impossible, to find a general metric of pairwise comparison that could be used for global analysis (187). Moreover, to be useful, strategies require of methods capable of organizing the comparative data within an evolutionary perspective.…”

Characterization of the Molecular Basis of Group II Intron RNA Recognition by CRS1-CRM Domains

“…Their similar architecture, in which several ␣ and ␤ domains are attached to a basic ␤␣␤␤ core, namely ␤␣-(␤␣␤␤) in the CRM/Alba family (5-8) and (␤␣␤␤)-␣␤ in RRM domains (37)(38)(39), may suggest either convergent evolution to carry out similar functions (e.g. the binding or folding of large catalytic RNAs), or co-evolution of the CRM and RRM domains from an ancient RNA-binding ␤␣␤␤-type protein ancestor, as has been previously suggested for ␣␤-type RNA-binding proteins (40,41). Indeed, when assayed for its binding activity, the CRM3 ␤␣␤␤ core was found to associate with atpF intron RNA in the low micromolar range (supplemental Fig.…”