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The observation of evolutionary interaction pattern pairs in membrane proteins.

Grunert S, Labudde D - BMC Struct. Biol. (2015)

Bottom Line: The results indicate a good agreement with recent studies.This points to their general importance for α-helical membrane protein structure formation and interaction mediation.In the process, no fundamentally energetic approaches of previous published works are considered.

View Article: PubMed Central - PubMed

Affiliation: Hochschule Mittweida, University of Applied Sciences, Technikumplatz 17, Mittweida, 09648, Germany. sgrunert@hs-mittweida.de.

ABSTRACT

Background: Over the last two decades, many approaches have been developed in bioinformatics that aim at one of the most promising, yet unsolved problems in modern life sciences--prediction of structural features of a protein. Such tasks addressed to transmembrane protein structures provide valuable knowledge about their three-dimensional structure. For this reason, the analysis of membrane proteins is essential in genomic and proteomic-wide investigations. Thus, many in-silico approaches have been utilized extensively to gain crucial advances in understanding membrane protein structures and functions.

Results: It turned out that amino acid covariation within interacting sequence parts, extracted from a evolutionary sequence record of α-helical membrane proteins, can be used for structure prediction. In a recent study we discussed the significance of short membrane sequence motifs widely present in nature that act as stabilizing 'building blocks' during protein folding and in retaining the three-dimensional fold. In this work, we used motif data to define evolutionary interaction pattern pairs. These were obtained from different pattern alignments and were used to evaluate which coupling mechanisms the evolution provides. It can be shown that short interaction patterns of homologous sequence records are membrane protein family-specific signatures. These signatures can provide valuable information for structure prediction and protein classification. The results indicate a good agreement with recent studies.

Conclusions: Generally, it can be shown how the evolution contributes to realize covariation within discriminative interaction patterns to maintain structure and function. This points to their general importance for α-helical membrane protein structure formation and interaction mediation. In the process, no fundamentally energetic approaches of previous published works are considered. The low-cost rapid computational methods postulated in this work provides valuable information to classify unknown α-helical transmembrane proteins and to determine their structural similarity.

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Mutation interaction types. Four mutation interaction types are present. Labelled spheres indicate which amino acid at specified position is present related to PDB-Id. A: Simple evolutionary replacements (red) around the blue and green interacting residue spheres. B: Interacting AL9 motifs (blue and green) with evolutionary residue substitution without loss of interaction. Mutations at one or at both interaction partner are possible. B1: Asp 115 at the second position of AL9-motif pattern representative AD 115GIMIGTL interacts with Ala 91 or Pro 91 of AL9-motif pattern representative A[SD] 85WLFTT[AP] 91LL. This is made possible by the same orientation of Ala 91 and Pro 91 towards its interacting counterpart. B2: Analogously, fourth position of AL9-motif pattern representative AFT[MA] 56YLSMLL is designed variable with Ala 56 or Met 56 and interacts with Asp 85 or Ser 85 reason by same orientation in space. C: If contact information will be lost by mutation, the responsible destabilizing amino acid will be compensated by another position, in order to maintain attractive residue pair interaction [16]. C1/C2: Ile 148 and Val 148 at fifth position of AL9-motif pattern representative AMLY[VIA] 148LYVL (blue) are able to interact with Ala 114 at sixth position of LI8-motif representative LAL 111VGA114DGI (green). C3: Mutation with Ala 148 causes that contact will be lost reason by to short distance to Ala 114 counterpart. Here, Leu 111 at third position of LI8-motif compensates the destabilizing amino acid. Evolution aims at maintaining stabilizing interactions. D: Trp 137/142 is an evolutionary coupling residue which interacts with Ile 129 or Val 124 by full changeable residue environment around Trp 137/142. This means that the evolutionary degree of freedom allows it to change all variable positions of an interacting pattern by keeping the conserved interaction residue.
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Fig3: Mutation interaction types. Four mutation interaction types are present. Labelled spheres indicate which amino acid at specified position is present related to PDB-Id. A: Simple evolutionary replacements (red) around the blue and green interacting residue spheres. B: Interacting AL9 motifs (blue and green) with evolutionary residue substitution without loss of interaction. Mutations at one or at both interaction partner are possible. B1: Asp 115 at the second position of AL9-motif pattern representative AD 115GIMIGTL interacts with Ala 91 or Pro 91 of AL9-motif pattern representative A[SD] 85WLFTT[AP] 91LL. This is made possible by the same orientation of Ala 91 and Pro 91 towards its interacting counterpart. B2: Analogously, fourth position of AL9-motif pattern representative AFT[MA] 56YLSMLL is designed variable with Ala 56 or Met 56 and interacts with Asp 85 or Ser 85 reason by same orientation in space. C: If contact information will be lost by mutation, the responsible destabilizing amino acid will be compensated by another position, in order to maintain attractive residue pair interaction [16]. C1/C2: Ile 148 and Val 148 at fifth position of AL9-motif pattern representative AMLY[VIA] 148LYVL (blue) are able to interact with Ala 114 at sixth position of LI8-motif representative LAL 111VGA114DGI (green). C3: Mutation with Ala 148 causes that contact will be lost reason by to short distance to Ala 114 counterpart. Here, Leu 111 at third position of LI8-motif compensates the destabilizing amino acid. Evolution aims at maintaining stabilizing interactions. D: Trp 137/142 is an evolutionary coupling residue which interacts with Ile 129 or Val 124 by full changeable residue environment around Trp 137/142. This means that the evolutionary degree of freedom allows it to change all variable positions of an interacting pattern by keeping the conserved interaction residue.

Mentions: Incidentally, for reasons of incomplete TMPad information not all position specific mutations are an integral part of our EIPPs. Only EIPP related mutations were collected if any contact could be detected from TMPad. Regarding this tree information, different known structures of PF01036 were analysed for EIPPs. The investigation of Rhodopsin-like proteins represents a major subject of research. Here different structure-function studies were performed [32,33]. Further, the investigation of active core fluctuations, the folding core and kinetics and the involved residues have been treated extensively in previous studies [34-36]. In this work, Bacteriorhodopsin-like protein structures were used to evaluate the derived EIPPs. Representatives of the statistically most interacting motifs were searched. Furthermore, long motif XYn (n=9) representative patterns show a greater tendency to interact more frequently than short ones, because of the larger number of possible residue-residue interaction combinations. The examples given in Figure 3 show, how different EIPPs comprise structural tasks and spatial interactions. Specifically, the evolution presents how EIPPs contribute to emerge different evolutionary mutation types. These types describe the sequence variability on a closer way, which has no significant influence on the protein structure and function.Figure 3


The observation of evolutionary interaction pattern pairs in membrane proteins.

Grunert S, Labudde D - BMC Struct. Biol. (2015)

Mutation interaction types. Four mutation interaction types are present. Labelled spheres indicate which amino acid at specified position is present related to PDB-Id. A: Simple evolutionary replacements (red) around the blue and green interacting residue spheres. B: Interacting AL9 motifs (blue and green) with evolutionary residue substitution without loss of interaction. Mutations at one or at both interaction partner are possible. B1: Asp 115 at the second position of AL9-motif pattern representative AD 115GIMIGTL interacts with Ala 91 or Pro 91 of AL9-motif pattern representative A[SD] 85WLFTT[AP] 91LL. This is made possible by the same orientation of Ala 91 and Pro 91 towards its interacting counterpart. B2: Analogously, fourth position of AL9-motif pattern representative AFT[MA] 56YLSMLL is designed variable with Ala 56 or Met 56 and interacts with Asp 85 or Ser 85 reason by same orientation in space. C: If contact information will be lost by mutation, the responsible destabilizing amino acid will be compensated by another position, in order to maintain attractive residue pair interaction [16]. C1/C2: Ile 148 and Val 148 at fifth position of AL9-motif pattern representative AMLY[VIA] 148LYVL (blue) are able to interact with Ala 114 at sixth position of LI8-motif representative LAL 111VGA114DGI (green). C3: Mutation with Ala 148 causes that contact will be lost reason by to short distance to Ala 114 counterpart. Here, Leu 111 at third position of LI8-motif compensates the destabilizing amino acid. Evolution aims at maintaining stabilizing interactions. D: Trp 137/142 is an evolutionary coupling residue which interacts with Ile 129 or Val 124 by full changeable residue environment around Trp 137/142. This means that the evolutionary degree of freedom allows it to change all variable positions of an interacting pattern by keeping the conserved interaction residue.
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Related In: Results  -  Collection

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Fig3: Mutation interaction types. Four mutation interaction types are present. Labelled spheres indicate which amino acid at specified position is present related to PDB-Id. A: Simple evolutionary replacements (red) around the blue and green interacting residue spheres. B: Interacting AL9 motifs (blue and green) with evolutionary residue substitution without loss of interaction. Mutations at one or at both interaction partner are possible. B1: Asp 115 at the second position of AL9-motif pattern representative AD 115GIMIGTL interacts with Ala 91 or Pro 91 of AL9-motif pattern representative A[SD] 85WLFTT[AP] 91LL. This is made possible by the same orientation of Ala 91 and Pro 91 towards its interacting counterpart. B2: Analogously, fourth position of AL9-motif pattern representative AFT[MA] 56YLSMLL is designed variable with Ala 56 or Met 56 and interacts with Asp 85 or Ser 85 reason by same orientation in space. C: If contact information will be lost by mutation, the responsible destabilizing amino acid will be compensated by another position, in order to maintain attractive residue pair interaction [16]. C1/C2: Ile 148 and Val 148 at fifth position of AL9-motif pattern representative AMLY[VIA] 148LYVL (blue) are able to interact with Ala 114 at sixth position of LI8-motif representative LAL 111VGA114DGI (green). C3: Mutation with Ala 148 causes that contact will be lost reason by to short distance to Ala 114 counterpart. Here, Leu 111 at third position of LI8-motif compensates the destabilizing amino acid. Evolution aims at maintaining stabilizing interactions. D: Trp 137/142 is an evolutionary coupling residue which interacts with Ile 129 or Val 124 by full changeable residue environment around Trp 137/142. This means that the evolutionary degree of freedom allows it to change all variable positions of an interacting pattern by keeping the conserved interaction residue.
Mentions: Incidentally, for reasons of incomplete TMPad information not all position specific mutations are an integral part of our EIPPs. Only EIPP related mutations were collected if any contact could be detected from TMPad. Regarding this tree information, different known structures of PF01036 were analysed for EIPPs. The investigation of Rhodopsin-like proteins represents a major subject of research. Here different structure-function studies were performed [32,33]. Further, the investigation of active core fluctuations, the folding core and kinetics and the involved residues have been treated extensively in previous studies [34-36]. In this work, Bacteriorhodopsin-like protein structures were used to evaluate the derived EIPPs. Representatives of the statistically most interacting motifs were searched. Furthermore, long motif XYn (n=9) representative patterns show a greater tendency to interact more frequently than short ones, because of the larger number of possible residue-residue interaction combinations. The examples given in Figure 3 show, how different EIPPs comprise structural tasks and spatial interactions. Specifically, the evolution presents how EIPPs contribute to emerge different evolutionary mutation types. These types describe the sequence variability on a closer way, which has no significant influence on the protein structure and function.Figure 3

Bottom Line: The results indicate a good agreement with recent studies.This points to their general importance for α-helical membrane protein structure formation and interaction mediation.In the process, no fundamentally energetic approaches of previous published works are considered.

View Article: PubMed Central - PubMed

Affiliation: Hochschule Mittweida, University of Applied Sciences, Technikumplatz 17, Mittweida, 09648, Germany. sgrunert@hs-mittweida.de.

ABSTRACT

Background: Over the last two decades, many approaches have been developed in bioinformatics that aim at one of the most promising, yet unsolved problems in modern life sciences--prediction of structural features of a protein. Such tasks addressed to transmembrane protein structures provide valuable knowledge about their three-dimensional structure. For this reason, the analysis of membrane proteins is essential in genomic and proteomic-wide investigations. Thus, many in-silico approaches have been utilized extensively to gain crucial advances in understanding membrane protein structures and functions.

Results: It turned out that amino acid covariation within interacting sequence parts, extracted from a evolutionary sequence record of α-helical membrane proteins, can be used for structure prediction. In a recent study we discussed the significance of short membrane sequence motifs widely present in nature that act as stabilizing 'building blocks' during protein folding and in retaining the three-dimensional fold. In this work, we used motif data to define evolutionary interaction pattern pairs. These were obtained from different pattern alignments and were used to evaluate which coupling mechanisms the evolution provides. It can be shown that short interaction patterns of homologous sequence records are membrane protein family-specific signatures. These signatures can provide valuable information for structure prediction and protein classification. The results indicate a good agreement with recent studies.

Conclusions: Generally, it can be shown how the evolution contributes to realize covariation within discriminative interaction patterns to maintain structure and function. This points to their general importance for α-helical membrane protein structure formation and interaction mediation. In the process, no fundamentally energetic approaches of previous published works are considered. The low-cost rapid computational methods postulated in this work provides valuable information to classify unknown α-helical transmembrane proteins and to determine their structural similarity.

Show MeSH