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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.


Related in: MedlinePlus

Dependence of mfDCA values on distance.As expected, the magnitude of the mfDCA coupling decayed with the increase of the distance between the pair of interacting positions. Both non-sequon related (A) and sequon to non-sequon related interactions (B) showed a rather regular pattern of interaction strength inversely proportional to the distance. Sequon to sequon interactions magnitude fell off with the distance faster (C) and were almost entirely contained within a radius of 15Å consistent with contact interactions between glycans. A small group of inter-sequon interactions occurred at a distance more than 20 Å.
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pone.0128664.g007: Dependence of mfDCA values on distance.As expected, the magnitude of the mfDCA coupling decayed with the increase of the distance between the pair of interacting positions. Both non-sequon related (A) and sequon to non-sequon related interactions (B) showed a rather regular pattern of interaction strength inversely proportional to the distance. Sequon to sequon interactions magnitude fell off with the distance faster (C) and were almost entirely contained within a radius of 15Å consistent with contact interactions between glycans. A small group of inter-sequon interactions occurred at a distance more than 20 Å.

Mentions: As expected, the mfDCA values decreased with the increase of the interatomic distances (Fig 7). SRP couplings decreased faster than the rest. The large radius of the glycans increases the distance, at which direct contacts would affect fitness Thus, it seemed that SRP coevolution was predominantly affected by direct contacts between amino acid residues or by the attached glycans. At the same time, several long range interactions were found too (Fig 8, S3 File). These included E293–N462, E293–N355, S334–D230, R444–D230, R444–Q363 and N197–N276. Most of them involved the outer domain SRP E293, S334 and R444 and linked them to membrane proximal regions (D230, N355 and N462), and the core near V4/V5 (Q363 and N355). Although these long range interactions were few, they represented homotypic pairing between low entropy positions (both frequent and rare) but not highly variable sequon positions (Fig 9 and Table 1). The long range homotypic frequent to frequent and rare to rare sequon pairings together with much closer frequent to rare interdependencies confirmed that rare sequons most probably are versions of the nearby frequent ones and probably have a similar role. Homotypic coupling is predominant also for variable loops high entropy SRP, which are mostly connected to their neighbors.


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

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

Dependence of mfDCA values on distance.As expected, the magnitude of the mfDCA coupling decayed with the increase of the distance between the pair of interacting positions. Both non-sequon related (A) and sequon to non-sequon related interactions (B) showed a rather regular pattern of interaction strength inversely proportional to the distance. Sequon to sequon interactions magnitude fell off with the distance faster (C) and were almost entirely contained within a radius of 15Å consistent with contact interactions between glycans. A small group of inter-sequon interactions occurred at a distance more than 20 Å.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0128664.g007: Dependence of mfDCA values on distance.As expected, the magnitude of the mfDCA coupling decayed with the increase of the distance between the pair of interacting positions. Both non-sequon related (A) and sequon to non-sequon related interactions (B) showed a rather regular pattern of interaction strength inversely proportional to the distance. Sequon to sequon interactions magnitude fell off with the distance faster (C) and were almost entirely contained within a radius of 15Å consistent with contact interactions between glycans. A small group of inter-sequon interactions occurred at a distance more than 20 Å.
Mentions: As expected, the mfDCA values decreased with the increase of the interatomic distances (Fig 7). SRP couplings decreased faster than the rest. The large radius of the glycans increases the distance, at which direct contacts would affect fitness Thus, it seemed that SRP coevolution was predominantly affected by direct contacts between amino acid residues or by the attached glycans. At the same time, several long range interactions were found too (Fig 8, S3 File). These included E293–N462, E293–N355, S334–D230, R444–D230, R444–Q363 and N197–N276. Most of them involved the outer domain SRP E293, S334 and R444 and linked them to membrane proximal regions (D230, N355 and N462), and the core near V4/V5 (Q363 and N355). Although these long range interactions were few, they represented homotypic pairing between low entropy positions (both frequent and rare) but not highly variable sequon positions (Fig 9 and Table 1). The long range homotypic frequent to frequent and rare to rare sequon pairings together with much closer frequent to rare interdependencies confirmed that rare sequons most probably are versions of the nearby frequent ones and probably have a similar role. Homotypic coupling is predominant also for variable loops high entropy SRP, which are mostly connected to their neighbors.

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.


Related in: MedlinePlus