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

Kirioka, Takuya; Aumpuchin, Panyavut; Kikuchi, Takeshi

doi:10.4172/jpb.1000446

Cited by 11 publications

(27 citation statements)

References 39 publications

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“…It should be noticed that we consider the autonomous folding of a protein and compare our results to available experimental data. We have confirmed in previous studies that our prediction methods successfully extract the folding properties that well to the data from experimental analyses of following proteins: fatty acid binding proteins, 19 globin-like fold proteins, 20 IgG binding and albumin binding domains, 21 Ig-like fold proteins, 22 ferredoxin-like fold proteins, 23 beta-trafoil fold proteins, 24 and lysozyme-like superfamily proteins. 25 2 | MATERIAL AND METHOD…”

Section: Introductionsupporting

confidence: 79%

“…Such regions correspond to experimental analyzes of protein folding mechanisms. [19][20][21][22][23][24][25] The details of this method were described in the Supporting Information (Figures S1 and S2).…”

Section: Average Distance Map Analysis Methodsmentioning

confidence: 99%

“…In this study, we flanked a sequence of 20 glycine residues at both the N-and C-termini to avoid too high fluctuations at the ends as shown in previous studies. [22][23][24]29 A peak is regarded as a significant site for an initial folding event.…”

Section: Average Distance Map Analysis Methodsmentioning

confidence: 99%

“…The conserved hydrophobic residue site corresponds to a ratio of more than 90% of residues at an aligned site (red line). [20][21][22][23][24][25] It is interesting to find that the conserved part of this histogram appears at the key strands, that is, β-strands 3, 4, 5, and 6. Thus, the key strands and the conserved hydrophobic residues tend to be included in PdCRs evolutionarily.…”

Section: Evolutionary Analysis Of Titin Domainsmentioning

confidence: 98%

“…The F-value analysis could extract the residues with high possibility to make a contact in an early event as confirmed in previous studies. [20][21][22][23][24][25] In this study, we performed the F-value analyses of TI In TI I27, the peaks from the F-value plots were determined at positions G16, K35, E51, and H61 ( Figure 3A), and the hydrophobic residues within AE5 residues of the peak are considered as a residue which might significantly important in the initial hydrophobic collapse event (show by red dot on the F-value plots). 25 Interestingly, the core residues, F21, W34, and L58, are located near the peaks within AE5 residues.…”

Section: The Contact Frequency Analyses Based On Interresidue Averamentioning

confidence: 99%

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Prediction of folding mechanisms for Ig‐like beta sandwich proteins based on inter‐residue average distance statistics methods

Aumpuchin

Kikuchi

2018

Proteins

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To understand the folding mechanism of a protein is one of the goals in bioinformatics study.Nowadays, it is enigmatic and difficult to extract folding information from amino acid sequence using standard bioinformatics techniques or even experimental protocols which can be time consuming. To overcome these problems, we aim to extract the initial folding unit for titin protein (Ig and fnIII domains) by means of inter-residue average distance statistics, Average Distance Map (ADM) and contact frequency analysis (F-value). TI I27 and TNfn3 domains are used to represent the Ig-domain and fnIII-domain, respectively. Beta-strands 2, 3, 5, and 6 are significant for the initial folding processes of TI I27. The central strands of TNfn3 were predicted as a primary folding segment. Known 3D structure and unknown 3D structure domains were investigated by structure or non-structure based multiple sequence alignment, respectively, to learn the conserved hydrophobic residues and predicted compact region relevant to evolution. Our results show good correspondence to experimental data, phi-value and protection factor from H-D exchange experiments. The significance of conserved hydrophobic residues near F-value peaks for structural stability using hydrophobic packing is confirmed. Our prediction methods once again could extract a folding mechanism only knowing the amino acid sequence. K E Y W O R D S evolutionary analysis, folding, Ig-like beta sandwich proteins, inter-residue average distance statistics, titin

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Section: Introductionsupporting

confidence: 79%

Section: Average Distance Map Analysis Methodsmentioning

confidence: 99%

Section: Average Distance Map Analysis Methodsmentioning

confidence: 99%

Section: Evolutionary Analysis Of Titin Domainsmentioning

confidence: 98%

Section: The Contact Frequency Analyses Based On Interresidue Averamentioning

confidence: 99%

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Prediction of folding mechanisms for Ig‐like beta sandwich proteins based on inter‐residue average distance statistics methods

Aumpuchin

Kikuchi

2018

Proteins

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Conserved buried water molecules enable the β‐trefoil architecture

Blaber

2020

Protein Science

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Available high‐resolution crystal structures for the family of β‐trefoil proteins in the structural databank were queried for buried waters. Such waters were classified as either: (a) unique to a particular domain, family, or superfamily or (b) conserved among all β‐trefoil folds. Three buried waters conserved among all β‐trefoil folds were identified. These waters are related by the threefold rotational pseudosymmetry characteristic of this protein architecture (representing three instances of an identical structural environment within each repeating trefoil‐fold motif). The structural properties of this buried water are remarkable and include: residing in a cavity space no larger than a single water molecule, exhibiting a positional uncertainty (i.e., normalized B‐factor) substantially lower than the average Cα atom, providing essentially ideal H‐bonding geometry with three solvent‐inaccessible main chain groups, simultaneously serving as a bridging H‐bond for three different β‐strands at a point of secondary structure divergence, and orienting conserved hydrophobic side chains to form a nascent core‐packing group. Other published work supports an interpretation that these interactions are key to the formation of an efficient folding nucleus and folded thermostability. The fundamental threefold symmetric structural element of the β‐trefoil fold is therefore, surprisingly, a buried water molecule.

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Cooperative hydrophobic core interactions in the β‐trefoil architecture

Blaber

2021

Protein Science

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Symmetric protein architectures have a compelling aesthetic that suggests a plausible evolutionary process (i.e., gene duplication/fusion) yielding complex architecture from a simpler structural motif. Furthermore, symmetry inspires a practical approach to computational protein design that substantially reduces the combinatorial explosion problem, and may provide practical solutions for structure optimization. Despite such broad relevance, the role of structural symmetry in the key area of hydrophobic core‐packing cooperativity has not been adequately studied. In the present report, the threefold rotational symmetry intrinsic to the β‐trefoil architecture is shown to form a geometric basis for highly‐cooperative core‐packing interactions that both stabilize the local repeating motif and promote oligomerization/long‐range contacts in the folding process. Symmetry in the β‐trefoil structure also permits tolerance towards mutational drift that involves a structural quasi‐equivalence at several key core positions.

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

Cited by 11 publications

References 39 publications

Prediction of folding mechanisms for Ig‐like beta sandwich proteins based on inter‐residue average distance statistics methods

Prediction of folding mechanisms for Ig‐like beta sandwich proteins based on inter‐residue average distance statistics methods

Conserved buried water molecules enable the β‐trefoil architecture

Cooperative hydrophobic core interactions in the β‐trefoil architecture

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