Limits...
The Patterns of Coevolution in Clade B HIV Envelope's N-Glycosylation Sites.

Garimalla S, Kieber-Emmons T, Pashov AD - PLoS ONE (2015)

Bottom Line: Indications of pressure to preserve the evolving glycan shield are seen as well as strong dependencies between the majority of the potential N-glycosylation sites and the rest of the structure.The map we propose fills the gap in previous attempts to tease out sequon evolution by providing a more general molecular context.Thus, it will help design strategies guiding HIV gp120 evolution in a rational way.

View Article: PubMed Central - PubMed

Affiliation: University of Michigan Health System, Ann Arbor, MI, United States of America.

ABSTRACT
The co-evolution of the potential N-glycosylation sites of HIV Clade B gp120 was mapped onto the coevolution network of the protein structure using mean field direct coupling analysis (mfDCA). This was possible for 327 positions with suitable entropy and gap content. Indications of pressure to preserve the evolving glycan shield are seen as well as strong dependencies between the majority of the potential N-glycosylation sites and the rest of the structure. These findings indicate that although mainly an adaptation against antibody neutralization, the evolving glycan shield is structurally related to the core polypeptide, which, thus, is also under pressure to reflect the changes in the N-glycosylation. The map we propose fills the gap in previous attempts to tease out sequon evolution by providing a more general molecular context. Thus, it will help design strategies guiding HIV gp120 evolution in a rational way.

No MeSH data available.


Graph representation of the interacting pairs.(A) The layout was constructed using Force Atlas 2 algorithm (Gephi). The size of the label (amino acid position number) correlates with the degree of the respective node in the graph. The modularity analysis of the graph yielded 7 modularity classes—color coded. The mapping of the major modularity classes on the 2B4C gp120 structure (B—stereo view) shows a good agreement with secondary and tertiary structure units. The V3 (green), V4 (red) and V5 (ochre) loops overlap with three separate classes, while V1/V2 fall into a class colored yellow. The logic of the visualization algorithm pulls cliques to the periphery and in the case of gp120 these are represented most notably by V4 and V5 and, to a lesser extent—V1/V2. Even the spatial relationships between these structures are marked although projecting on 2D plane distorts them. The only major discrepancy is the position of the V3 loop, but it is important to note that 2B4C structure represents the bound conformation of gp120 and the V3 loop in the unbound state seems to be positioned rather where the graph suggests. Thus the layout algorithm used reconstructed the main structural relations in gp120 based on the mfDCA coupling analysis.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4482261&req=5

pone.0128664.g003: Graph representation of the interacting pairs.(A) The layout was constructed using Force Atlas 2 algorithm (Gephi). The size of the label (amino acid position number) correlates with the degree of the respective node in the graph. The modularity analysis of the graph yielded 7 modularity classes—color coded. The mapping of the major modularity classes on the 2B4C gp120 structure (B—stereo view) shows a good agreement with secondary and tertiary structure units. The V3 (green), V4 (red) and V5 (ochre) loops overlap with three separate classes, while V1/V2 fall into a class colored yellow. The logic of the visualization algorithm pulls cliques to the periphery and in the case of gp120 these are represented most notably by V4 and V5 and, to a lesser extent—V1/V2. Even the spatial relationships between these structures are marked although projecting on 2D plane distorts them. The only major discrepancy is the position of the V3 loop, but it is important to note that 2B4C structure represents the bound conformation of gp120 and the V3 loop in the unbound state seems to be positioned rather where the graph suggests. Thus the layout algorithm used reconstructed the main structural relations in gp120 based on the mfDCA coupling analysis.

Mentions: The set of relations was further visualized as an undirected weighted graph with nodes representing the sequence positions and edges representing the significant couplings (Fig 3A). The graph consisted of a major component containing all analyzed positions except for 415 as an isolated node and 241 and 496, which formed the minor component. The mean degree was 5.92 meaning that on the average each position was coupled to approximately 6 others. The network diameter was 8. Thus, if the shortest paths between the aa positions in this direct couplings graph represent potential allosteric paths the longest among them is a chain of 8 residues.


The Patterns of Coevolution in Clade B HIV Envelope's N-Glycosylation Sites.

Garimalla S, Kieber-Emmons T, Pashov AD - PLoS ONE (2015)

Graph representation of the interacting pairs.(A) The layout was constructed using Force Atlas 2 algorithm (Gephi). The size of the label (amino acid position number) correlates with the degree of the respective node in the graph. The modularity analysis of the graph yielded 7 modularity classes—color coded. The mapping of the major modularity classes on the 2B4C gp120 structure (B—stereo view) shows a good agreement with secondary and tertiary structure units. The V3 (green), V4 (red) and V5 (ochre) loops overlap with three separate classes, while V1/V2 fall into a class colored yellow. The logic of the visualization algorithm pulls cliques to the periphery and in the case of gp120 these are represented most notably by V4 and V5 and, to a lesser extent—V1/V2. Even the spatial relationships between these structures are marked although projecting on 2D plane distorts them. The only major discrepancy is the position of the V3 loop, but it is important to note that 2B4C structure represents the bound conformation of gp120 and the V3 loop in the unbound state seems to be positioned rather where the graph suggests. Thus the layout algorithm used reconstructed the main structural relations in gp120 based on the mfDCA coupling analysis.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4482261&req=5

pone.0128664.g003: Graph representation of the interacting pairs.(A) The layout was constructed using Force Atlas 2 algorithm (Gephi). The size of the label (amino acid position number) correlates with the degree of the respective node in the graph. The modularity analysis of the graph yielded 7 modularity classes—color coded. The mapping of the major modularity classes on the 2B4C gp120 structure (B—stereo view) shows a good agreement with secondary and tertiary structure units. The V3 (green), V4 (red) and V5 (ochre) loops overlap with three separate classes, while V1/V2 fall into a class colored yellow. The logic of the visualization algorithm pulls cliques to the periphery and in the case of gp120 these are represented most notably by V4 and V5 and, to a lesser extent—V1/V2. Even the spatial relationships between these structures are marked although projecting on 2D plane distorts them. The only major discrepancy is the position of the V3 loop, but it is important to note that 2B4C structure represents the bound conformation of gp120 and the V3 loop in the unbound state seems to be positioned rather where the graph suggests. Thus the layout algorithm used reconstructed the main structural relations in gp120 based on the mfDCA coupling analysis.
Mentions: The set of relations was further visualized as an undirected weighted graph with nodes representing the sequence positions and edges representing the significant couplings (Fig 3A). The graph consisted of a major component containing all analyzed positions except for 415 as an isolated node and 241 and 496, which formed the minor component. The mean degree was 5.92 meaning that on the average each position was coupled to approximately 6 others. The network diameter was 8. Thus, if the shortest paths between the aa positions in this direct couplings graph represent potential allosteric paths the longest among them is a chain of 8 residues.

Bottom Line: Indications of pressure to preserve the evolving glycan shield are seen as well as strong dependencies between the majority of the potential N-glycosylation sites and the rest of the structure.The map we propose fills the gap in previous attempts to tease out sequon evolution by providing a more general molecular context.Thus, it will help design strategies guiding HIV gp120 evolution in a rational way.

View Article: PubMed Central - PubMed

Affiliation: University of Michigan Health System, Ann Arbor, MI, United States of America.

ABSTRACT
The co-evolution of the potential N-glycosylation sites of HIV Clade B gp120 was mapped onto the coevolution network of the protein structure using mean field direct coupling analysis (mfDCA). This was possible for 327 positions with suitable entropy and gap content. Indications of pressure to preserve the evolving glycan shield are seen as well as strong dependencies between the majority of the potential N-glycosylation sites and the rest of the structure. These findings indicate that although mainly an adaptation against antibody neutralization, the evolving glycan shield is structurally related to the core polypeptide, which, thus, is also under pressure to reflect the changes in the N-glycosylation. The map we propose fills the gap in previous attempts to tease out sequon evolution by providing a more general molecular context. Thus, it will help design strategies guiding HIV gp120 evolution in a rational way.

No MeSH data available.