Dataset Information

Detecting remote homologues using scoring matrices calculated from the estimation of amino acid substitution rates of beta-barrel membrane proteins.

ABSTRACT: Beta-barrel membrane proteins (MP) are found in Gram-negative bacteria, mitochondria and chloroplasts. They play important roles in metabolism of bacteria, where they are involved in transport of solutes in and out of the cell. Beta-barrel proteins may also act as proteases, lipases and may be important for cell-cell adhesion. Currently, there are about 30 non-redundant solved structures of beta-barrels. Although the number of b-barrel folds is fairly small, it is possible to expand the amount of available structural information by homology modeling using existing structures as templates. The scope of structure prediction may be widened by finding remote homologues of the existing structures. To improve the sensitivity of the database searches and the quality of sequence alignments, we first study evolutionary history of transmembrane segments of 7 beta-barrel membrane proteins by estimating substitution rates with a Bayesian Monte Carlo approach. Next, we calculate amino acid substitution matrices, beta-barrel Transmembrane scoring Matrices (bbTM), specifically tuned for TM regions, which can be used to detect remote homologues. We then test bbTM matrices by comparing their performance with membrane-protein derived scoring matrices PHAT and SLIM. Our results demonstrate that bbTM matrices have higher selectivity towards transmembrane beta-barrel proteins and may be used with higher confidence in database searches for remote homologues of this class of proteins.

SUBMITTER: Jimenez-Morales D

PROVIDER: S-EPMC2630510 | biostudies-literature | 2008

REPOSITORIES: biostudies-literature

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Detecting remote homologues using scoring matrices calculated from the estimation of amino acid substitution rates of beta-barrel membrane proteins.

Jimenez-Morales David D Adamian Larisa L Liang Jie J

Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference 20080101

Beta-barrel membrane proteins (MP) are found in Gram-negative bacteria, mitochondria and chloroplasts. They play important roles in metabolism of bacteria, where they are involved in transport of solutes in and out of the cell. Beta-barrel proteins may also act as proteases, lipases and may be important for cell-cell adhesion. Currently, there are about 30 non-redundant solved structures of beta-barrels. Although the number of b-barrel folds is fairly small, it is possible to expand the amount o ...[more]

PMID: 19162917

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Project description:β-barrel membrane proteins play an important role in controlling the exchange and transport of ions and organic molecules across bacterial and mitochondrial outer membranes. They are also major regulators of apoptosis and are important determinants of bacterial virulence. In contrast to β-helical membrane proteins, their evolutionary pattern of residue substitutions has not been quantified, and there are no scoring matrices appropriate for their detection through sequence alignment. Using a Bayesian Monte Carlo estimator, we have calculated the instantaneous substitution rates of transmembrane domains of bacterial β-barrel membrane proteins. The scoring matrices constructed from the estimated rates, called bbTM for β-barrel Transmembrane Matrices, improve significantly the sensitivity in detecting homologs of β-barrel membrane proteins, while avoiding erroneous selection of both soluble proteins and other membrane proteins of similar composition. The estimated evolutionary patterns are general and can detect β-barrel membrane proteins very remote from those used for substitution rate estimation. Furthermore, despite the separation of 2-3 billion years since the proto-mitochondrion entered the proto-eukaryotic cell, mitochondria outer membrane proteins in eukaryotes can also be detected accurately using these scoring matrices derived from bacteria. This is consistent with the suggestion that there is no eukaryote-specific signals for translocation. With these matrices, remote homologs of β-barrel membrane proteins with known structures can be reliably detected at genome scale, allowing construction of high quality structural models of their transmembrane domains, at the rate of 131 structures per template protein. The scoring matrices will be useful for identification, classification, and functional inference of membrane proteins from genome and metagenome sequencing projects. The estimated substitution pattern will also help to identify key elements important for the structural and functional integrity of β-barrel membrane proteins, and will aid in the design of mutagenesis studies.

Dataset Information

Detecting remote homologues using scoring matrices calculated from the estimation of amino acid substitution rates of beta-barrel membrane proteins.

Publications

Detecting remote homologues using scoring matrices calculated from the estimation of amino acid substitution rates of beta-barrel membrane proteins.

Similar Datasets

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