Limits...
Bioinformatics and Moonlighting Proteins.

Hernández S, Franco L, Calvo A, Ferragut G, Hermoso A, Amela I, Gómez A, Querol E, Cedano J - Front Bioeng Biotechnol (2015)

Bottom Line: Remote homology search by Psi-Blast combined with data from interactomics databases (PPIs) has the best performance.Structural information and mutation correlation analysis can help us to map the functional sites.Mutation correlation analysis can only be used in very specific situations - it requires the existence of multialigned family protein sequences - but can suggest how the evolutionary process of second function acquisition took place.

View Article: PubMed Central - PubMed

Affiliation: Institut de Biotecnologia i Biomedicina and Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona , Barcelona , Spain.

ABSTRACT
Multitasking or moonlighting is the capability of some proteins to execute two or more biochemical functions. Usually, moonlighting proteins are experimentally revealed by serendipity. For this reason, it would be helpful that Bioinformatics could predict this multifunctionality, especially because of the large amounts of sequences from genome projects. In the present work, we analyze and describe several approaches that use sequences, structures, interactomics, and current bioinformatics algorithms and programs to try to overcome this problem. Among these approaches are (a) remote homology searches using Psi-Blast, (b) detection of functional motifs and domains, (c) analysis of data from protein-protein interaction databases (PPIs), (d) match the query protein sequence to 3D databases (i.e., algorithms as PISITE), and (e) mutation correlation analysis between amino acids by algorithms as MISTIC. Programs designed to identify functional motif/domains detect mainly the canonical function but usually fail in the detection of the moonlighting one, Pfam and ProDom being the best methods. Remote homology search by Psi-Blast combined with data from interactomics databases (PPIs) has the best performance. Structural information and mutation correlation analysis can help us to map the functional sites. Mutation correlation analysis can only be used in very specific situations - it requires the existence of multialigned family protein sequences - but can suggest how the evolutionary process of second function acquisition took place. The multitasking protein database MultitaskProtDB (http://wallace.uab.es/multitask/), previously published by our group, has been used as a benchmark for the all of the analyses.

No MeSH data available.


An example of second function mapping using sequence approaches. In (A), a moonlighting protein sequence (red) is aligned with ClustalW to another moonlighting protein sequence of a different organism (black) that was found after a BLASTP analysis. In (B), the same approach is used and the moonlighting protein sequence (red) is aligned with two monofunctional proteins (green/blue), each one in a region of the moonlighting protein; therefore, mapping the canonical and moonlighting functions of the original protein.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4478894&req=5

Figure 1: An example of second function mapping using sequence approaches. In (A), a moonlighting protein sequence (red) is aligned with ClustalW to another moonlighting protein sequence of a different organism (black) that was found after a BLASTP analysis. In (B), the same approach is used and the moonlighting protein sequence (red) is aligned with two monofunctional proteins (green/blue), each one in a region of the moonlighting protein; therefore, mapping the canonical and moonlighting functions of the original protein.

Mentions: Blast, and especially Psi-Blast, can detect a number of multitasking proteins indicated as those having more than one stretch aligned to different targets. For instance, Figure 1 shows an example for the protein 2-amino-4-hydroxy-6-hydroxymethyldihydropterine pyrophosphokinase (HPPK) and dihydropteroate synthase (DHPS). This example can also represent a case for gene fusions leading to a multitasking protein.


Bioinformatics and Moonlighting Proteins.

Hernández S, Franco L, Calvo A, Ferragut G, Hermoso A, Amela I, Gómez A, Querol E, Cedano J - Front Bioeng Biotechnol (2015)

An example of second function mapping using sequence approaches. In (A), a moonlighting protein sequence (red) is aligned with ClustalW to another moonlighting protein sequence of a different organism (black) that was found after a BLASTP analysis. In (B), the same approach is used and the moonlighting protein sequence (red) is aligned with two monofunctional proteins (green/blue), each one in a region of the moonlighting protein; therefore, mapping the canonical and moonlighting functions of the original protein.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4478894&req=5

Figure 1: An example of second function mapping using sequence approaches. In (A), a moonlighting protein sequence (red) is aligned with ClustalW to another moonlighting protein sequence of a different organism (black) that was found after a BLASTP analysis. In (B), the same approach is used and the moonlighting protein sequence (red) is aligned with two monofunctional proteins (green/blue), each one in a region of the moonlighting protein; therefore, mapping the canonical and moonlighting functions of the original protein.
Mentions: Blast, and especially Psi-Blast, can detect a number of multitasking proteins indicated as those having more than one stretch aligned to different targets. For instance, Figure 1 shows an example for the protein 2-amino-4-hydroxy-6-hydroxymethyldihydropterine pyrophosphokinase (HPPK) and dihydropteroate synthase (DHPS). This example can also represent a case for gene fusions leading to a multitasking protein.

Bottom Line: Remote homology search by Psi-Blast combined with data from interactomics databases (PPIs) has the best performance.Structural information and mutation correlation analysis can help us to map the functional sites.Mutation correlation analysis can only be used in very specific situations - it requires the existence of multialigned family protein sequences - but can suggest how the evolutionary process of second function acquisition took place.

View Article: PubMed Central - PubMed

Affiliation: Institut de Biotecnologia i Biomedicina and Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona , Barcelona , Spain.

ABSTRACT
Multitasking or moonlighting is the capability of some proteins to execute two or more biochemical functions. Usually, moonlighting proteins are experimentally revealed by serendipity. For this reason, it would be helpful that Bioinformatics could predict this multifunctionality, especially because of the large amounts of sequences from genome projects. In the present work, we analyze and describe several approaches that use sequences, structures, interactomics, and current bioinformatics algorithms and programs to try to overcome this problem. Among these approaches are (a) remote homology searches using Psi-Blast, (b) detection of functional motifs and domains, (c) analysis of data from protein-protein interaction databases (PPIs), (d) match the query protein sequence to 3D databases (i.e., algorithms as PISITE), and (e) mutation correlation analysis between amino acids by algorithms as MISTIC. Programs designed to identify functional motif/domains detect mainly the canonical function but usually fail in the detection of the moonlighting one, Pfam and ProDom being the best methods. Remote homology search by Psi-Blast combined with data from interactomics databases (PPIs) has the best performance. Structural information and mutation correlation analysis can help us to map the functional sites. Mutation correlation analysis can only be used in very specific situations - it requires the existence of multialigned family protein sequences - but can suggest how the evolutionary process of second function acquisition took place. The multitasking protein database MultitaskProtDB (http://wallace.uab.es/multitask/), previously published by our group, has been used as a benchmark for the all of the analyses.

No MeSH data available.