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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.


Distribution of potential N-glycosylation sites (sequons).Overall there were 94 positions, which represented less than 99% conserved sequon related asparagine residues. This excluded the two highly conserved positions N88 and N262. The lower bound was 16 sequences with sequon at the site—the threshold for random occurrence of sequons. As it has been demonstrated earlier, these sequons grouped further in several groups. Relating the frequency of the sequon in each of those positions to the entropy (variability) of the site (A), it was possible to outline three distinct groups. Some sites were represented more often than not by a sequon and were designated “Frequent”. Other, on the contrary, represented sequons in the minority of the sequences (although not random) and were designated “Rare”. The third group represented high entropy sites, in which neither the sequon related N nor other residues predominated—these were designated “Variable”. Mapping these three classes on the primary structure of gp120 (B) not surprisingly showed that “Variable” sequons were found in the variable regions, “Frequent” and “Rare” sequons appeared mostly on the constant and the “Rare” sequons were very often in close proximity to at least one sequon from the other classes.
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pone.0128664.g004: Distribution of potential N-glycosylation sites (sequons).Overall there were 94 positions, which represented less than 99% conserved sequon related asparagine residues. This excluded the two highly conserved positions N88 and N262. The lower bound was 16 sequences with sequon at the site—the threshold for random occurrence of sequons. As it has been demonstrated earlier, these sequons grouped further in several groups. Relating the frequency of the sequon in each of those positions to the entropy (variability) of the site (A), it was possible to outline three distinct groups. Some sites were represented more often than not by a sequon and were designated “Frequent”. Other, on the contrary, represented sequons in the minority of the sequences (although not random) and were designated “Rare”. The third group represented high entropy sites, in which neither the sequon related N nor other residues predominated—these were designated “Variable”. Mapping these three classes on the primary structure of gp120 (B) not surprisingly showed that “Variable” sequons were found in the variable regions, “Frequent” and “Rare” sequons appeared mostly on the constant and the “Rare” sequons were very often in close proximity to at least one sequon from the other classes.

Mentions: Relating position entropy to frequency of sequon related asparagine grouped the potential N-glycosylation sites in 3 groups:—frequent (13 N and 10 S/T positions), rare (20 N and 14 S/T positions) and highly variable (31 N and 6 S/T positions) (Fig 4A). Some N positions coincide with S/T positions of an adjacent sequon so S/T positions are fewer. This classification omits the highly conserved positions N88 and N262, which were filtered initially. Since all the sequons represent only potential glycosylation sites from here on we shall omit the word potential but it will be implied all through this report. The complete list of the analyzed sequon positions is given in S1 Dataset. The variable positions are characteristic of the variable loops V1/V2, V4 and V5. The rare sequons occur actually in the close vicinity of frequent ones not only in the structure but also topologically in the graph. Therefore, most probably the rare sequons represent functionally equivalent variants of the frequent ones (Fig 4B).


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

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

Distribution of potential N-glycosylation sites (sequons).Overall there were 94 positions, which represented less than 99% conserved sequon related asparagine residues. This excluded the two highly conserved positions N88 and N262. The lower bound was 16 sequences with sequon at the site—the threshold for random occurrence of sequons. As it has been demonstrated earlier, these sequons grouped further in several groups. Relating the frequency of the sequon in each of those positions to the entropy (variability) of the site (A), it was possible to outline three distinct groups. Some sites were represented more often than not by a sequon and were designated “Frequent”. Other, on the contrary, represented sequons in the minority of the sequences (although not random) and were designated “Rare”. The third group represented high entropy sites, in which neither the sequon related N nor other residues predominated—these were designated “Variable”. Mapping these three classes on the primary structure of gp120 (B) not surprisingly showed that “Variable” sequons were found in the variable regions, “Frequent” and “Rare” sequons appeared mostly on the constant and the “Rare” sequons were very often in close proximity to at least one sequon from the other classes.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0128664.g004: Distribution of potential N-glycosylation sites (sequons).Overall there were 94 positions, which represented less than 99% conserved sequon related asparagine residues. This excluded the two highly conserved positions N88 and N262. The lower bound was 16 sequences with sequon at the site—the threshold for random occurrence of sequons. As it has been demonstrated earlier, these sequons grouped further in several groups. Relating the frequency of the sequon in each of those positions to the entropy (variability) of the site (A), it was possible to outline three distinct groups. Some sites were represented more often than not by a sequon and were designated “Frequent”. Other, on the contrary, represented sequons in the minority of the sequences (although not random) and were designated “Rare”. The third group represented high entropy sites, in which neither the sequon related N nor other residues predominated—these were designated “Variable”. Mapping these three classes on the primary structure of gp120 (B) not surprisingly showed that “Variable” sequons were found in the variable regions, “Frequent” and “Rare” sequons appeared mostly on the constant and the “Rare” sequons were very often in close proximity to at least one sequon from the other classes.
Mentions: Relating position entropy to frequency of sequon related asparagine grouped the potential N-glycosylation sites in 3 groups:—frequent (13 N and 10 S/T positions), rare (20 N and 14 S/T positions) and highly variable (31 N and 6 S/T positions) (Fig 4A). Some N positions coincide with S/T positions of an adjacent sequon so S/T positions are fewer. This classification omits the highly conserved positions N88 and N262, which were filtered initially. Since all the sequons represent only potential glycosylation sites from here on we shall omit the word potential but it will be implied all through this report. The complete list of the analyzed sequon positions is given in S1 Dataset. The variable positions are characteristic of the variable loops V1/V2, V4 and V5. The rare sequons occur actually in the close vicinity of frequent ones not only in the structure but also topologically in the graph. Therefore, most probably the rare sequons represent functionally equivalent variants of the frequent ones (Fig 4B).

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.