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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.


Mapping the sequon related positions of the potential N-glycosylation sites on the graph of mfDCA couplings.(A) “Variable”—ochre for N and magenta for S/T, “Frequent”—red –N, bordeaux –S/T and “Rare”—green—N, blue—S/T for. The P3 (S/T) positions appear less than the P1 (N) positions because N was selected to represent the position when the P1 and P3 overlapped for adjacent sequons. Overall, the sequons formed two connected subgraphs leaving out positions 49, 51, 130 and 199. The variable V1/V2, V4 and V5 regions represented tight cliques in the large subpgraph while p301–304 formed the smaller subgraph. The ego network (all immediately connected positions) of the sequons (B), was a highly connected and included a large part of the non-sequon positions. Therefore, it seems most of the sequons are closely interrelated but do not segregate from the rest of the structure. Even the variable loops cliques are bound by numerous relations to the rest of the graph. (C)–The sequon related positions mapped on the 2B4C structure in stereo view are color coded for their epistatic coupling to other sequon positions (red), to non-sequon positions (blue) or to both equally (yellow). If the proportion of sequon position related couplings is above 0.5 the color is orange, if less than 0.5 –gray. The predominantly sequon coupled positions are found in V4 but mostly in V1/V2 (not shown) as well as 293 and 446 in the middle of the cluster on the outer domain. The most “structure related” sequon positions are 130, 199, 304, 368, 467 and 241.
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pone.0128664.g005: Mapping the sequon related positions of the potential N-glycosylation sites on the graph of mfDCA couplings.(A) “Variable”—ochre for N and magenta for S/T, “Frequent”—red –N, bordeaux –S/T and “Rare”—green—N, blue—S/T for. The P3 (S/T) positions appear less than the P1 (N) positions because N was selected to represent the position when the P1 and P3 overlapped for adjacent sequons. Overall, the sequons formed two connected subgraphs leaving out positions 49, 51, 130 and 199. The variable V1/V2, V4 and V5 regions represented tight cliques in the large subpgraph while p301–304 formed the smaller subgraph. The ego network (all immediately connected positions) of the sequons (B), was a highly connected and included a large part of the non-sequon positions. Therefore, it seems most of the sequons are closely interrelated but do not segregate from the rest of the structure. Even the variable loops cliques are bound by numerous relations to the rest of the graph. (C)–The sequon related positions mapped on the 2B4C structure in stereo view are color coded for their epistatic coupling to other sequon positions (red), to non-sequon positions (blue) or to both equally (yellow). If the proportion of sequon position related couplings is above 0.5 the color is orange, if less than 0.5 –gray. The predominantly sequon coupled positions are found in V4 but mostly in V1/V2 (not shown) as well as 293 and 446 in the middle of the cluster on the outer domain. The most “structure related” sequon positions are 130, 199, 304, 368, 467 and 241.

Mentions: Mapping the sequon related positions on the coevolution graph reiterated their grouping in variable loop and “constant” part ones (Fig 5A). The SRP alone formed a rather connected network leaving out the V3 sequons (N301/ T303 and N302/R304) and the N386/T388 sequon while the inner domain positions T49, T51, N130 and S199 were not dependent on any other sequon. The sequon ego network (all positions immediately linked to a SRP) contained the larger part of the non-sequon positions (144 of 233 nodes–Fig 5B) and represented a highly connected network. Even the variable loop cliques are bound by numerous relations to the rest of the graph. The SRP that had relation to non-sequon positions were 85 of 94. Interestingly, 6 of 8 SRP that related only to other SRP were found in V1/V2 and the other two are S364 and N406 in V4. The sequon unaccounted for is the isolated node T415. The sequons that had predominantly non-sequon dependencies were found on the constant part in close vicinity to the loops (Fig 5C). These latter positions were also related to the most connected core of the co-evolutionary network.


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

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

Mapping the sequon related positions of the potential N-glycosylation sites on the graph of mfDCA couplings.(A) “Variable”—ochre for N and magenta for S/T, “Frequent”—red –N, bordeaux –S/T and “Rare”—green—N, blue—S/T for. The P3 (S/T) positions appear less than the P1 (N) positions because N was selected to represent the position when the P1 and P3 overlapped for adjacent sequons. Overall, the sequons formed two connected subgraphs leaving out positions 49, 51, 130 and 199. The variable V1/V2, V4 and V5 regions represented tight cliques in the large subpgraph while p301–304 formed the smaller subgraph. The ego network (all immediately connected positions) of the sequons (B), was a highly connected and included a large part of the non-sequon positions. Therefore, it seems most of the sequons are closely interrelated but do not segregate from the rest of the structure. Even the variable loops cliques are bound by numerous relations to the rest of the graph. (C)–The sequon related positions mapped on the 2B4C structure in stereo view are color coded for their epistatic coupling to other sequon positions (red), to non-sequon positions (blue) or to both equally (yellow). If the proportion of sequon position related couplings is above 0.5 the color is orange, if less than 0.5 –gray. The predominantly sequon coupled positions are found in V4 but mostly in V1/V2 (not shown) as well as 293 and 446 in the middle of the cluster on the outer domain. The most “structure related” sequon positions are 130, 199, 304, 368, 467 and 241.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0128664.g005: Mapping the sequon related positions of the potential N-glycosylation sites on the graph of mfDCA couplings.(A) “Variable”—ochre for N and magenta for S/T, “Frequent”—red –N, bordeaux –S/T and “Rare”—green—N, blue—S/T for. The P3 (S/T) positions appear less than the P1 (N) positions because N was selected to represent the position when the P1 and P3 overlapped for adjacent sequons. Overall, the sequons formed two connected subgraphs leaving out positions 49, 51, 130 and 199. The variable V1/V2, V4 and V5 regions represented tight cliques in the large subpgraph while p301–304 formed the smaller subgraph. The ego network (all immediately connected positions) of the sequons (B), was a highly connected and included a large part of the non-sequon positions. Therefore, it seems most of the sequons are closely interrelated but do not segregate from the rest of the structure. Even the variable loops cliques are bound by numerous relations to the rest of the graph. (C)–The sequon related positions mapped on the 2B4C structure in stereo view are color coded for their epistatic coupling to other sequon positions (red), to non-sequon positions (blue) or to both equally (yellow). If the proportion of sequon position related couplings is above 0.5 the color is orange, if less than 0.5 –gray. The predominantly sequon coupled positions are found in V4 but mostly in V1/V2 (not shown) as well as 293 and 446 in the middle of the cluster on the outer domain. The most “structure related” sequon positions are 130, 199, 304, 368, 467 and 241.
Mentions: Mapping the sequon related positions on the coevolution graph reiterated their grouping in variable loop and “constant” part ones (Fig 5A). The SRP alone formed a rather connected network leaving out the V3 sequons (N301/ T303 and N302/R304) and the N386/T388 sequon while the inner domain positions T49, T51, N130 and S199 were not dependent on any other sequon. The sequon ego network (all positions immediately linked to a SRP) contained the larger part of the non-sequon positions (144 of 233 nodes–Fig 5B) and represented a highly connected network. Even the variable loop cliques are bound by numerous relations to the rest of the graph. The SRP that had relation to non-sequon positions were 85 of 94. Interestingly, 6 of 8 SRP that related only to other SRP were found in V1/V2 and the other two are S364 and N406 in V4. The sequon unaccounted for is the isolated node T415. The sequons that had predominantly non-sequon dependencies were found on the constant part in close vicinity to the loops (Fig 5C). These latter positions were also related to the most connected core of the co-evolutionary network.

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.