MHJ_0461 is a multifunctional leucine aminopeptidase on the surface of Mycoplasma hyopneumoniae

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Aminopeptidases are part of the arsenal of virulence factors produced by bacterial pathogens that inactivate host immune peptides. Mycoplasma hyopneumoniae is a genome-reduced pathogen of swine that lacks the genetic repertoire to synthesize amino acids and relies on the host for availability of amino acids for growth. M. hyopneumoniae recruits plasmin(ogen) onto its cell surface via the P97 and P102 adhesins and the glutamyl aminopeptidase MHJ_0125. Plasmin plays an important role in regulating the inflammatory response in the lungs of pigs infected with M. hyopneumoniae. We show that recombinant MHJ_0461 (rMHJ_0461) functions as a leucine aminopeptidase (LAP) with broad substrate specificity for leucine, alanine, phenylalanine, methionine and arginine and that MHJ_0461 resides on the surface of M. hyopneumoniae. rMHJ_0461 also binds heparin, plasminogen and foreign DNA. Plasminogen bound to rMHJ_0461 was readily converted to plasmin in the presence of tPA. Computational modelling identified putative DNA and heparin-binding motifs on solvent-exposed sites around a large pore on the LAP hexamer. We conclude that MHJ_0461 is a LAP that moonlights as a multifunctional adhesin on the cell surface of M. hyopneumoniae.

Related collections

Most cited references 64

Record: found
Abstract: found
Article: not found

Conservation and prediction of solvent accessibility in protein families.

B Rost, C. Sander (1994)

Currently, the prediction of three-dimensional (3D) protein structure from sequence alone is an exceedingly difficult task. As an intermediate step, a much simpler task has been pursued extensively: predicting 1D strings of secondary structure. Here, we present an analysis of another 1D projection from 3D structure: the relative solvent accessibility of each residue. We show that solvent accessibility is less conserved in 3D homologues than is secondary structure, and hence is predicted less accurately from automatic homology modeling; the correlation coefficient of relative solvent accessibility between 3D homologues is only 0.77, and the average accuracy of predictions based on sequence alignments is only 0.68. The latter number provides an effective upper limit on the accuracy of predicting accessibility from sequence when homology modeling is not possible. We introduce a neural network system that predicts relative solvent accessibility (projected onto ten discrete states) using evolutionary profiles of amino acid substitutions derived from multiple sequence alignments. Evaluated in a cross-validation test on 238 unique proteins, the correlation between predicted and observed relative accessibility is 0.54. Interpreted in terms of a three-state (buried, intermediate, exposed) description of relative accessibility, the fraction of correctly predicted residue states is about 58%. In absolute terms this accuracy appears poor, but given the relatively low conservation of accessibility in 3D families, the network system is not far from its likely optimal performance. The most reliably predicted fraction of the residues (50%) is predicted as accurately as by automatic homology modeling. Prediction is best for buried residues, e.g., 86% of the completely buried sites are correctly predicted as having 0% relative accessibility.

0 comments Cited 134 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Swine and poultry pathogens: the complete genome sequences of two strains of Mycoplasma hyopneumoniae and a strain of Mycoplasma synoviae.

Ana Tereza R. Vasconcelos, Henrique B Ferreira, Cristiano V Bizarro … (2005)

This work reports the results of analyses of three complete mycoplasma genomes, a pathogenic (7448) and a nonpathogenic (J) strain of the swine pathogen Mycoplasma hyopneumoniae and a strain of the avian pathogen Mycoplasma synoviae; the genome sizes of the three strains were 920,079 bp, 897,405 bp, and 799,476 bp, respectively. These genomes were compared with other sequenced mycoplasma genomes reported in the literature to examine several aspects of mycoplasma evolution. Strain-specific regions, including integrative and conjugal elements, and genome rearrangements and alterations in adhesin sequences were observed in the M. hyopneumoniae strains, and all of these were potentially related to pathogenicity. Genomic comparisons revealed that reduction in genome size implied loss of redundant metabolic pathways, with maintenance of alternative routes in different species. Horizontal gene transfer was consistently observed between M. synoviae and Mycoplasma gallisepticum. Our analyses indicated a likely transfer event of hemagglutinin-coding DNA sequences from M. gallisepticum to M. synoviae.

0 comments Cited 100 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Statistical potentials for fold assessment.

Francisco Melo, Roberto Sanchez, Andrej Sali (2002)

A protein structure model generally needs to be evaluated to assess whether or not it has the correct fold. To improve fold assessment, four types of a residue-level statistical potential were optimized, including distance-dependent, contact, Phi/Psi dihedral angle, and accessible surface statistical potentials. Approximately 10,000 test models with the correct and incorrect folds were built by automated comparative modeling of protein sequences of known structure. The criterion used to discriminate between the correct and incorrect models was the Z-score of the model energy. The performance of a Z-score was determined as a function of many variables in the derivation and use of the corresponding statistical potential. The performance was measured by the fractions of the correctly and incorrectly assessed test models. The most discriminating combination of any one of the four tested potentials is the sum of the normalized distance-dependent and accessible surface potentials. The distance-dependent potential that is optimal for assessing models of all sizes uses both C(alpha) and C(beta) atoms as interaction centers, distinguishes between all 20 standard residue types, has the distance range of 30 A, and is derived and used by taking into account the sequence separation of the interacting atom pairs. The terms for the sequentially local interactions are significantly less informative than those for the sequentially nonlocal interactions. The accessible surface potential that is optimal for assessing models of all sizes uses C(beta) atoms as interaction centers and distinguishes between all 20 standard residue types. The performance of the tested statistical potentials is not likely to improve significantly with an increase in the number of known protein structures used in their derivation. The parameters of fold assessment whose optimal values vary significantly with model size include the size of the known protein structures used to derive the potential and the distance range of the accessible surface potential. Fold assessment by statistical potentials is most difficult for the very small models. This difficulty presents a challenge to fold assessment in large-scale comparative modeling, which produces many small and incomplete models. The results described in this study provide a basis for an optimal use of statistical potentials in fold assessment.

0 comments Cited 99 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Journal

Journal ID (nlm-ta): Open Biol

Journal ID (iso-abbrev): Open Biol

Journal ID (publisher-id): RSOB

Journal ID (hwp): royopenbio

Title: Open Biology

Publisher: The Royal Society

ISSN (Electronic): 2046-2441

Publication date (Print): January 2015

Publication date PMC-release: January 2015

Volume: 5

Issue: 1

Electronic Location Identifier: 140175

Affiliations

[1 ]The ithree institute, University of Technology , Sydney, PO Box 123, Broadway, New South Wales 2007, Australia

[2 ]Proteomics Core Facility, University of Technology , Sydney, PO Box 123, Broadway, New South Wales 2007, Australia

[3 ]NSW Department of Primary Industries, Private Bag 4008, Narellan, New South Wales 2567, Australia

Author notes

e-mail: steven.djordjevic@ 123456uts.edu.au

Article

Publisher ID: rsob140175

DOI: 10.1098/rsob.140175

PMC ID: 4313372

PubMed ID: 25589579

SO-VID: 45f576ed-c414-40e0-afcb-ab13110300c2

License:

© 2015 The Authors. Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited.

History

Date received : 1 October 2014

Date accepted : 15 December 2014

Custom metadata

cover-date January 2015

ScienceOpen disciplines: Life sciences

Keywords: adhesin,dna-binding protein,plasminogen-binding protein,heparin-binding protein,leucine aminopeptidase,moonlighting protein

Data availability:

ScienceOpen disciplines: Life sciences

Keywords: adhesin, dna-binding protein, plasminogen-binding protein, heparin-binding protein, leucine aminopeptidase, moonlighting protein

MHJ_0461 is a multifunctional leucine aminopeptidase on the surface of Mycoplasma hyopneumoniae

Read this article at

Abstract

Related collections

Evolutionary Cell Biology

Most cited references 64

Conservation and prediction of solvent accessibility in protein families.

Swine and poultry pathogens: the complete genome sequences of two strains of Mycoplasma hyopneumoniae and a strain of Mycoplasma synoviae.

Statistical potentials for fold assessment.

Author and article information

Journal

Affiliations

Author notes

Article

History

Categories

Custom metadata

Comments

Comment on this article

Similar content 266

Cited by 25

Most referenced authors 1,259