Structure is three to ten times more conserved than sequence—A study of structural response in protein cores

Illergård, Kristoffer; Ardell, David H.; Elofsson, Arne

doi:10.1002/prot.22458

Cited by 410 publications

(367 citation statements)

References 27 publications

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“…Because the structures of proteins are more conserved than their sequences (28), structure determination can provide more definitive information that establishes the functional relatedness of two proteins and also their possible cellular functions. In the present work, we solved the structure of the CT670 protein, which is the first structure of a YscO homolog determined for any species.…”

Section: Discussionmentioning

confidence: 99%

Structure and Protein-Protein Interaction Studies on Chlamydia trachomatis Protein CT670 (YscO Homolog)

et al. 2010

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Comparative genomic studies have identified many proteins that are found only in various Chlamydiae species and exhibit no significant sequence similarity to any protein in organisms that do not belong to this group. The CT670 protein of Chlamydia trachomatis is one of the proteins whose genes are in one of the type III secretion gene clusters but whose cellular functions are not known. CT670 shares several characteristics with the YscO protein of Yersinia pestis, including the neighboring genes, size, charge, and secondary structure, but the structures and/or functions of these proteins remain to be determined. Although a BLAST search with CT670 did not identify YscO as a related protein, our analysis indicated that these two proteins exhibit significant sequence similarity. In this paper, we report that the CT670 crystal, solved at a resolution of 2 Å, consists of a single coiled coil containing just two long helices. Gel filtration and analytical ultracentrifugation studies showed that in solution CT670 exists in both monomeric and dimeric forms and that the monomer predominates at lower protein concentrations. We examined the interaction of CT670 with many type III secretion system-related proteins (viz., CT091, CT665, CT666, CT667, CT668, CT669, CT671, CT672, and CT673) by performing bacterial two-hybrid assays. In these experiments, CT670 was found to interact only with the CT671 protein (YscP homolog), whose gene is immediately downstream of ct670. A specific interaction between CT670 and CT671 was also observed when affinity chromatography pull-down experiments were performed. These results suggest that CT670 and CT671 are putative homologs of the YcoO and YscP proteins, respectively, and that they likely form a chaperone-effector pair.Chlamydiae are obligate intracellular bacteria that infect a variety of eukaryotes, including humans, animals, insects, and free-living amoebae (8, 31, 51). They are highly pathogenic and cause genital tract, ocular, and respiratory infections in humans (9, 55). A key characteristic of Chlamydiae is their biphasic developmental cycle, in which the bacteria alternate between two morphologies: the elementary body and the reticulate body (1, 31). The Chlamydiae species, like many other Gram-negative pathogenic bacteria, contain a type III secretion (T3S) system, which plays a major role in their pathogenicity (4, 7, 44). This key system aids pathogenicity by exporting bacterial proteins, termed effectors, into the host cell via a syringe-like nanomachine called an injectisome (4, 7). Once secreted into the host cell, these effectors may manipulate host cell functions to the advantage of the pathogen (44, 54).Because of the unique chlamydial developmental cycle currently there are no tractable methods for genetic manipulation of these organisms (25,49). Detailed bioinformatic investigations have identified approximately 200 proteins unique to various taxonomic levels of the Chlamydiae phylum (19, 21). Included in this pool of proteins are proteins whose genes occur in chlamydi...

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Section: Discussionmentioning

confidence: 99%

Structure and Protein-Protein Interaction Studies on Chlamydia trachomatis Protein CT670 (YscO Homolog)

et al. 2010

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“…Even though there are tens of thousands of protein structures in the Protein Data Bank (PDB), 1 the structures they take are limited to some thousands of folds. 2,3 It is well known that protein structures are evolutionarily more conserved than sequences 4 and often sequences that have low sequence identity can share the same fold. 5 This leads to the concept of protein designability.…”

Section: Introductionmentioning

confidence: 99%

Exploration of the relationship between topology and designability of conformations

Leelananda

Towfic

Jernigan

et al. 2011

The Journal of Chemical Physics

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Protein structures are evolutionarily more conserved than sequences, and sequences with very low sequence identity frequently share the same fold. This leads to the concept of protein designability. Some folds are more designable and lots of sequences can assume that fold. Elucidating the relationship between protein sequence and the three-dimensional (3D) structure that the sequence folds into is an important problem in computational structural biology. Lattice models have been utilized in numerous studies to model protein folds and predict the designability of certain folds. In this study, all possible compact conformations within a set of two-dimensional and 3D lattice spaces are explored. Complementary interaction graphs are then generated for each conformation and are described using a set of graph features. The full HP sequence space for each lattice model is generated and contact energies are calculated by threading each sequence onto all the possible conformations. Unique conformation giving minimum energy is identified for each sequence and the number of sequences folding to each conformation (designability) is obtained. Machine learning algorithms are used to predict the designability of each conformation. We find that the highly designable structures can be distinguished from other non-designable conformations based on certain graphical geometric features of the interactions. This finding confirms the fact that the topology of a conformation is an important determinant of the extent of its designability and suggests that the interactions themselves are important for determining the designability.

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“…This result has been established based on the RMSD of aligned and superimposed protein cores (Chothia & Lesk, 1986) and later extended to other measures of structural change, allowing to quantify the statement that protein structure is more conserved than protein sequence (Illergård, Ardell & Elofsson, 2009).…”

Section: Protein Structure Classificationmentioning

confidence: 99%

Learning structural bioinformatics and evolution with a snake puzzle

Nido

Bachschmid-Romano

Bastolla

et al. 2016

PeerJ Computer Science

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We propose here a working unit for teaching basic concepts of structural bioinformatics and evolution through the example of a wooden snake puzzle, strikingly similar to toy models widely used in the literature of protein folding. In our experience, developed at a Master's course at the Universidad Autónoma de Madrid (Spain), the concreteness of this example helps to overcome difficulties caused by the interdisciplinary nature of this field and its high level of abstraction, in particular for students coming from traditional disciplines. The puzzle will allow us discussing a simple algorithm for finding folded solutions, through which we will introduce the concept of the configuration space and the contact matrix representation. This is a central tool for comparing protein structures, for studying simple models of protein energetics, and even for a qualitative discussion of folding kinetics, through the concept of the Contact Order. It also allows a simple representation of misfolded conformations and their free energy. These concepts will motivate evolutionary questions, which we will address by simulating a structurally constrained model of protein evolution, again modelled on the snake puzzle. In this way, we can discuss the analogy between evolutionary concepts and statistical mechanics that facilitates the understanding of both concepts. The proposed examples and literature are accessible, and we provide supplementary material (see 'Data Availability') to reproduce the numerical experiments. We also suggest possible directions to expand the unit. We hope that this work will further stimulate the adoption of games in teaching practice.

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Structure is three to ten times more conserved than sequence—A study of structural response in protein cores

Cited by 410 publications

References 27 publications

Structure and Protein-Protein Interaction Studies on Chlamydia trachomatis Protein CT670 (YscO Homolog)

Structure and Protein-Protein Interaction Studies on Chlamydia trachomatis Protein CT670 (YscO Homolog)

Exploration of the relationship between topology and designability of conformations

Learning structural bioinformatics and evolution with a snake puzzle

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