Symmetric Key Structural Residues in Symmetric Proteins with Beta-Trefoil Fold

Abstract

To understand how symmetric structures of many proteins are formed from asymmetric sequences, the proteins with two repeated beta-trefoil domains in Plant Cytotoxin B-chain family and all presently known beta-trefoil proteins are analyzed by structure-based multi-sequence alignments. The results show that all these proteins have similar key structural residues that are distributed symmetrically in their structures. These symmetric key structural residues are further analyzed in terms of inter-residues interaction numbers and B-factors. It is found that they can be distinguished from other residues and have significant propensities for structural framework. This indicates that these key structural residues may conduct the formation of symmetric structures although the sequences are asymmetric.

Detection of Folding Sites of β-Trefoil Fold Proteins Based on Amino Acid Sequence Analyses and Structure-Based Sequence Alignment

“…In the case of the β-strand 2, a conserved hydrophobic residue located in the N-terminal side is labeled as CHR-β2N and in the same way that in the C-terminal side is labeled as CHR-β2C. We confirm that these conserved hydrophobic residues correspond well to the conserved residues proposed by Murzin et al [4] and Feng et al [24]. Murzin et al defined the conservation of hydrophobic residues in two proteins from the Cytokine superfamily and one protein from STI-like superfamily.…”

“…This fact may indicate that these equally distributed hydrophobic residues need to form the symmetrical β-trefoil fold. Similar results were already obtained by Murzin et al [4] and Feng et al [24], and they revealed the relationships between conserved residues and 3D structures or interaction energies. Feng et al [24] also found "symmetric key structural residues" specific for the β-trefoil structure based on structure-based multiple sequence alignment of domains in five two-domain proteins with two β-trefoil structures.…”

“…Similar results were already obtained by Murzin et al [4] and Feng et al [24], and they revealed the relationships between conserved residues and 3D structures or interaction energies. Feng et al [24] also found "symmetric key structural residues" specific for the β-trefoil structure based on structure-based multiple sequence alignment of domains in five two-domain proteins with two β-trefoil structures. Furthermore, they elucidated that these symmetric key structural residues are wellconserved in the majority of β-trefoil proteins.…”

“…Li et al [22,23] and Feng et al [24] conducted multiple sequence alignments of selected β-trefoil proteins based on their 3D structures The separation of two residues along the sequence was taken into consideration as follows: M=1 when 1 ≤ k ≤ 8, M=2 when 9 ≤ k ≤ 20, M=3 when 21 ≤ k ≤ 30, M=4 when 31 ≤ k ≤ 40, and so on, where k=|i-j| and M is called as range. The average distances of all pairs of amino acid types were calculated in each range.…”

A 54-Kilodalton Protein Encoded by pBtoxis Is Required for Parasporal Body Structural Integrity in Bacillus thuringiensis subsp. israelensis

“…The connecting loops of the beta strands are known to vary in length and structure and provide specificity for binding to ligands such as other proteins, DNA, lipid membranes, and carbohydrates. The ricin-type beta-trefoil fold is found in a number of lectin-binding proteins, including ricin, hemagglutinin (HA)-related proteins including the HA33 protein of Clostridium botulinum and its homologue in Clostridium acetobutylicum, Cry (Cry41Ab1 and Cry42Ab1) and Cyt (Cyt1Ca) of B. thuringiensis, and the mosquitocidal toxins (Mtx) produced by Bacillus sphaericus during vegetative growth (6,7,9,12,13). The most characteristic feature of the beta-trefoil fold domain in lectin-binding proteins is the presence of three spatially separated glutamine-X-tryptophan QXW 3 repeats although the sequence is not absolutely conserved (13).…”