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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.


Comparison between mfDCA coupling values for Clade B gp120 based on the observed MSA or on the same MSA with scrambled columns.The amino acid residues in each column were randomly reordered and 100 different MSA with scrambled columns were thus generated. The mfDCA was performed on each of the 100 scrambled MSA and the maximal coupling values for each pair of positions (X) was related to the value from the observed MSA (Y). The maximum coupling value obtained after 100 permutations for each pair of positions was used as an upper limit of the random distribution of values for that pair. Thus, the dots above the diagonal represent the couplings, for which the actual mfDCA values were above the 99 percentile of the random coupling distribution. These mfDCA were considered significant and were used further in the analysis while the rest were replaced by zeros.
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pone.0128664.g001: Comparison between mfDCA coupling values for Clade B gp120 based on the observed MSA or on the same MSA with scrambled columns.The amino acid residues in each column were randomly reordered and 100 different MSA with scrambled columns were thus generated. The mfDCA was performed on each of the 100 scrambled MSA and the maximal coupling values for each pair of positions (X) was related to the value from the observed MSA (Y). The maximum coupling value obtained after 100 permutations for each pair of positions was used as an upper limit of the random distribution of values for that pair. Thus, the dots above the diagonal represent the couplings, for which the actual mfDCA values were above the 99 percentile of the random coupling distribution. These mfDCA were considered significant and were used further in the analysis while the rest were replaced by zeros.

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)

Comparison between mfDCA coupling values for Clade B gp120 based on the observed MSA or on the same MSA with scrambled columns.The amino acid residues in each column were randomly reordered and 100 different MSA with scrambled columns were thus generated. The mfDCA was performed on each of the 100 scrambled MSA and the maximal coupling values for each pair of positions (X) was related to the value from the observed MSA (Y). The maximum coupling value obtained after 100 permutations for each pair of positions was used as an upper limit of the random distribution of values for that pair. Thus, the dots above the diagonal represent the couplings, for which the actual mfDCA values were above the 99 percentile of the random coupling distribution. These mfDCA were considered significant and were used further in the analysis while the rest were replaced by zeros.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0128664.g001: Comparison between mfDCA coupling values for Clade B gp120 based on the observed MSA or on the same MSA with scrambled columns.The amino acid residues in each column were randomly reordered and 100 different MSA with scrambled columns were thus generated. The mfDCA was performed on each of the 100 scrambled MSA and the maximal coupling values for each pair of positions (X) was related to the value from the observed MSA (Y). The maximum coupling value obtained after 100 permutations for each pair of positions was used as an upper limit of the random distribution of values for that pair. Thus, the dots above the diagonal represent the couplings, for which the actual mfDCA values were above the 99 percentile of the random coupling distribution. These mfDCA were considered significant and were used further in the analysis while the rest were replaced by zeros.
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.