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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

The long range sequon to sequon interactions mapped onto the 2B4C structure.A—Stereo view perpendicular to the axis of the trimer, B—stereo view form the membrane proximal region along the axis of the trimer. The sequence related positions are color coded for their frequency/entropy (rare—green, variable—yellow, frequent—red). For a more precise inspection see the Chimera file (S3 File).
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pone.0128664.g008: The long range sequon to sequon interactions mapped onto the 2B4C structure.A—Stereo view perpendicular to the axis of the trimer, B—stereo view form the membrane proximal region along the axis of the trimer. The sequence related positions are color coded for their frequency/entropy (rare—green, variable—yellow, frequent—red). For a more precise inspection see the Chimera file (S3 File).

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)

The long range sequon to sequon interactions mapped onto the 2B4C structure.A—Stereo view perpendicular to the axis of the trimer, B—stereo view form the membrane proximal region along the axis of the trimer. The sequence related positions are color coded for their frequency/entropy (rare—green, variable—yellow, frequent—red). For a more precise inspection see the Chimera file (S3 File).
© Copyright Policy
Related In: Results  -  Collection

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

pone.0128664.g008: The long range sequon to sequon interactions mapped onto the 2B4C structure.A—Stereo view perpendicular to the axis of the trimer, B—stereo view form the membrane proximal region along the axis of the trimer. The sequence related positions are color coded for their frequency/entropy (rare—green, variable—yellow, frequent—red). For a more precise inspection see the Chimera file (S3 File).
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