Sequence and structure conservation in a protein core

Rodionov, Michael A.; Blundell, Tom L.

doi:10.1002/(sici)1097-0134(19981115)33:3<358::aid-prot5>3.3.co;2-s

Cited by 16 publications

(20 citation statements)

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“…Buried residues were defined as those having a solvent accessibility lower than 25 Å 2 . For most residues, this value indicates that 90% or more of the surface is buried (Rodionov and Blundell 1998).…”

Section: Structural Prediction and Homology Modelingmentioning

confidence: 99%

Metallochaperones and Metal-Transporting ATPases: A Comparative Analysis of Sequences and Structures

et al. 2002

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A comparative structural genomic analysis of a new class of metal-trafficking proteins can provide insights into the intracellular chemistry of reactive cofactors such as copper and zinc. Starting from the sequences of the metallochaperone Atx1 and from the first soluble domain of the copper-transporting ATPase Ccc2, both from yeast, a search on the available genomes was performed using a homology criterion and a metal-binding motif xЈ-xЉ-C-xٞ-x٣-C. By limiting ourselves to 20% identity with any of the proteins found, several soluble copper-transport proteins were identified, as well as soluble domains of membrane-bound ATPases. Structural models were calculated using high-resolution solution structures as templates, and the models were validated using statistical and energy criteria. Residue conservation and substitution have been interpreted and discussed in terms of structure-function relationship. The potential energy surfaces have been analyzed in terms of protein-protein interactions. We find that metallochaperones and their physiological partner ATPases from several phylogenetic kingdoms recognize one another, via an interplay of electrostatics, hydrogen bonding, and hydrophobic interactions, in a manner that precisely orients the metal-binding side chains for rapid metal transfer between otherwise tight binding sites. Finally, other putative metal-transport proteins are mentioned that have low homology and/or a different metal-binding consensus motif and that appear to use similar structures for recognition and transfer. This analysis highlights the wealth and the complexity of the field.

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Section: Structural Prediction and Homology Modelingmentioning

confidence: 99%

Metallochaperones and Metal-Transporting ATPases: A Comparative Analysis of Sequences and Structures

et al. 2002

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“…The variations that occur can be neutral: implying that they are irrelevant to the process of natural selection, crucial: meaning that they adapt the function of a protein to a given selective pressure, or can be somewhere in between. In general, a weak but statistically significant correlation is found between this sequence variability and a protein's solvent accessible surface area (Rodionov and Blundell, 1998). Interestingly, an apparent conservation of the three-dimensional pattern of conserved amino acids has been observed in several families of structurally homologous proteins that points to the existence of a folding nucleus (Mirny and Shakhnovich, 1999).…”

Section: Tubulin's Diversitymentioning

confidence: 99%

The evolution of the structure of tubulin and its potential consequences for the role and function of microtubules in cells and embryos

et al. 2006

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This paper discusses the results of homology modeling and resulting calculation of key structural and physical properties for close to 300 tubulin sequences, including α α α α α, β β β β β, γ γ γ γ γ, δ δ δ δ δ and ε ε ε ε ε -tubulins. The basis for our calculations was the structure of the tubulin dimer In addition to the general structural trends between tubulin isoforms, we have observed that the carboxy-termini of α α α α α and β β β β β-tubulin exists in at least two stable configurations, either projecting away from the tubulin (or microtubule) surface, or collapsed onto the surface. In the latter case, the carboxy-termini form a lattice distinctly different from that of the well-known A and B lattices formed by the tubulin subunits. However, this C-terminal lattice is indistinguishable from the lattice formed when the microtubule-associated protein tau binds to the microtubule surface. Finally, we have discussed how tubulin sequence diversity arose in evolution giving rise to its particular phylogeny and how it may be used in cell-and tissue-specific expression including embryonal development.

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“…The 3D-1D profiles are based on the so-called frozen approximation, i.e., the hypothesis that residue environments are conserved in protein with similar folds. This hypothesis has been recently questioned (48,49). The method described in this paper does not assume the frozen approximation (31,44), in that it designs a sequence profile for each model structure.…”

Section: Discussionmentioning

confidence: 99%

Improved recognition of native-like protein structures using a family of designed sequences

Koehl

Levitt²

2002

Proc. Natl. Acad. Sci. U.S.A.

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The goal of the inverse protein folding problem is to identify amino acid sequences that stabilize a given target protein conformation. Methods that attempt to solve this problem have proven useful for protein sequence design. Here we show that the same methods can provide valuable information for protein fold recognition and for ab initio protein structure prediction. We present a measure of the compatibility of a test sequence with a target model structure, based on computational protein design. The model structure is used as input to design a family of low free energy sequences, and these sequences are compared with the test sequence by using a metric in sequence space based on nearest-neighbor connectivity. We find that this measure is able to recognize the native fold of a myoglobin sequence among different globin folds. It is also powerful enough to recognize near-native protein structures among nonnative models.K nowing the structure of a protein is most useful for predicting, analyzing, and modifying its function. As it is not feasible to determine experimentally the structure of every protein, structure prediction has become central to the field of structural biology and more specifically to structural genomics. On the basis of their study of ribonuclease A (1), Anfinsen and coworkers provided the first clues that all of the information required for folding a protein is to be found in its sequence. Not long after this discovery, people took on the challenge of discovering the rules that allow the protein to fold. This problem is far from simple and has not yet been solved (2). Three major routes are usually considered paths to the solution: homology modeling, threading, and ab initio prediction. To study a protein with unknown conformation C, the first two methods follow the same scheme: a similar protein whose three-dimensional structure is known is identified, and this protein is used as a scaffold to generate a model for C. When the sequences of the two proteins are homologous (i.e., when they have an obvious common ancestry), sequence similarity is assumed to infer structural similarity (3, 4), and the method is then referred to as ''homology modeling.'' When the two sequences show no obvious evolutionary relationship, the method is referred to as ''fold recognition,'' which works by assessing the compatibility of the target sequence with each member of a library of known structures (5).Ab initio structure prediction methods try to build a model for the target protein structure without using a specific template protein. Most of these methods proceed by first generating a large collection of possible conformations (decoys), which are then searched with a scoring function to identify native or, more realistically, near-native conformations (6-9). This second step resembles the fold recognition problem, with the major difference that the library of folds considered includes computergenerated models instead of naturally occurring protein folds. In this paper, we show how recent developments of threading...

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Sequence and structure conservation in a protein core

Cited by 16 publications

References 0 publications

Metallochaperones and Metal-Transporting ATPases: A Comparative Analysis of Sequences and Structures

Metallochaperones and Metal-Transporting ATPases: A Comparative Analysis of Sequences and Structures

The evolution of the structure of tubulin and its potential consequences for the role and function of microtubules in cells and embryos

Improved recognition of native-like protein structures using a family of designed sequences

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