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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.


mfDCA coupling overlaid on the contact map of 2B4C.G structure.Significant couplings are marked with red dot to the background of gray level coded distances in angstroms. As expected, most of the significant values were along the diagonal indicating both primary and tertiary structure proximity. Those of highest intensity were aligned on the diagonal (not shown). A number of long range interactions (red dots in white areas) are observed also.
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pone.0128664.g002: mfDCA coupling overlaid on the contact map of 2B4C.G structure.Significant couplings are marked with red dot to the background of gray level coded distances in angstroms. As expected, most of the significant values were along the diagonal indicating both primary and tertiary structure proximity. Those of highest intensity were aligned on the diagonal (not shown). A number of long range interactions (red dots in white areas) are observed also.

Mentions: The network of coevolving positions was determined performing mfDCA on the multiple sequence alignment of 742 sequences with 327 considered positions. The mfDCA derived coupling values exceeding baseline (Fig 1) marked 969 significant of 53301 possible correlated pairs. The 2B4C structure contained 4356 pairs of positions with distances between the Cα atoms of less than 12 Å while the mfDCA algorithm highlighted 296 of those as functional couplings. As expected, the strongest interdependencies occurred for adjacent or nearby positions and also correlated inversely with the interatomic distances between the Cα atoms in the 2B4C structure (Fig 2 and S2 Fig). Nevertheless, 298 relations found by this analysis involved pairs at more than 12Å distance.


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

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

mfDCA coupling overlaid on the contact map of 2B4C.G structure.Significant couplings are marked with red dot to the background of gray level coded distances in angstroms. As expected, most of the significant values were along the diagonal indicating both primary and tertiary structure proximity. Those of highest intensity were aligned on the diagonal (not shown). A number of long range interactions (red dots in white areas) are observed also.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0128664.g002: mfDCA coupling overlaid on the contact map of 2B4C.G structure.Significant couplings are marked with red dot to the background of gray level coded distances in angstroms. As expected, most of the significant values were along the diagonal indicating both primary and tertiary structure proximity. Those of highest intensity were aligned on the diagonal (not shown). A number of long range interactions (red dots in white areas) are observed also.
Mentions: The network of coevolving positions was determined performing mfDCA on the multiple sequence alignment of 742 sequences with 327 considered positions. The mfDCA derived coupling values exceeding baseline (Fig 1) marked 969 significant of 53301 possible correlated pairs. The 2B4C structure contained 4356 pairs of positions with distances between the Cα atoms of less than 12 Å while the mfDCA algorithm highlighted 296 of those as functional couplings. As expected, the strongest interdependencies occurred for adjacent or nearby positions and also correlated inversely with the interatomic distances between the Cα atoms in the 2B4C structure (Fig 2 and S2 Fig). Nevertheless, 298 relations found by this analysis involved pairs at more than 12Å distance.

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.