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Flexibility and extracellular opening determine the interaction between ligands and insect sulfakinin receptors.

Yu N, Zotti MJ, Scheys F, Braz AS, Penna PH, Nachman RJ, Smagghe G - Sci Rep (2015)

Bottom Line: TcSKR1 contained a larger outer opening of the cavity than that in TcSKR2, which allows ligands a deep access into the cavity through cell membrane.Second, normal mode analysis revealed that TcSKR1 was more flexible than TcSKR2 during receptor-ligand interaction.Third, the sulfated SK (sSK) and sSK-related peptides were more potent than the nonsulfated SK, suggesting the importance of the sulfate moiety.

View Article: PubMed Central - PubMed

Affiliation: Department of Crop Protection, Faculty of Bioscience Engineering, Ghent University, 9000 Ghent, Belgium.

ABSTRACT
Despite their fundamental importance for growth, the mechanisms that regulate food intake are poorly understood. Our previous work demonstrated that insect sulfakinin (SK) signaling is involved in inhibiting feeding in an important model and pest insect, the red flour beetle Tribolium castaneum. Because the interaction of SK peptide and SK receptors (SKR) initiates the SK signaling, we have special interest on the structural factors that influence the SK-SKR interaction. First, the three-dimensional structures of the two T. castaneum SKRs (TcSKR1 and TcSKR2) were generated from molecular modeling and they displayed significance in terms of the outer opening of the cavity and protein flexibility. TcSKR1 contained a larger outer opening of the cavity than that in TcSKR2, which allows ligands a deep access into the cavity through cell membrane. Second, normal mode analysis revealed that TcSKR1 was more flexible than TcSKR2 during receptor-ligand interaction. Third, the sulfated SK (sSK) and sSK-related peptides were more potent than the nonsulfated SK, suggesting the importance of the sulfate moiety.

No MeSH data available.


Related in: MedlinePlus

Surface, ribbon, flexibility and interaction diagrams generated by normal mode analysis of TcSKR1 (A,C,E,G) and TcSKR2 (B,D,F,H) with nonsulfated sulfakinin (nsSK) peptide docked (colored by atom type). Cavities are colored by depth from blue (shallow) to orange (deep) in TcSKR1 (A) and TcSKR2 (B). The flexibility for each amino in SKR1 and SKR2 was retrieved from normal model analysis and the root-mean-square fluctuation (RMSF) was plotted onto each structure and colored from dark blue (rigid) to red (highly flexible) (E,F). The picture demonstrates a deep cavity in both structures but with an extended opening out cavity in SKR1 (C). The red arrows (F) indicate the most significant region responsible for reduction in outer openings of SKR2 cavity (D). The top view of TcSKR2 (D,F) displays a rigid core that restricts a larger outer opening of the cavity, which to some extend hinders a deeper intrusion of peptides into cavity. The figure C shows the larger outer opening of SKR1 allows the peptides to go deeper into cavity (see lupe detail). Docking of nsSK to TcSKR1 (C) and TcSKR2 (F). The clips show the binding of nsSK in both receptors through several hydrogen bonds colored by pink dashed lines. The residues are indicated by names and colored as light cyan.
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f2: Surface, ribbon, flexibility and interaction diagrams generated by normal mode analysis of TcSKR1 (A,C,E,G) and TcSKR2 (B,D,F,H) with nonsulfated sulfakinin (nsSK) peptide docked (colored by atom type). Cavities are colored by depth from blue (shallow) to orange (deep) in TcSKR1 (A) and TcSKR2 (B). The flexibility for each amino in SKR1 and SKR2 was retrieved from normal model analysis and the root-mean-square fluctuation (RMSF) was plotted onto each structure and colored from dark blue (rigid) to red (highly flexible) (E,F). The picture demonstrates a deep cavity in both structures but with an extended opening out cavity in SKR1 (C). The red arrows (F) indicate the most significant region responsible for reduction in outer openings of SKR2 cavity (D). The top view of TcSKR2 (D,F) displays a rigid core that restricts a larger outer opening of the cavity, which to some extend hinders a deeper intrusion of peptides into cavity. The figure C shows the larger outer opening of SKR1 allows the peptides to go deeper into cavity (see lupe detail). Docking of nsSK to TcSKR1 (C) and TcSKR2 (F). The clips show the binding of nsSK in both receptors through several hydrogen bonds colored by pink dashed lines. The residues are indicated by names and colored as light cyan.

Mentions: Figure 2 depicts the largest channel found in each modeled receptor that was calculated by MOLCAD. The cavities of both TcSKRs were similar in deepness from blue (shallow) to orange (deep). However, TcSKR2 had a narrow outer opening that prevented a deep intrusion of ligands into protein volume (Fig. 2D). In contrast, TcSKR1 exhibited a cavity similar in depth, but with a much larger outer opening than TcSKR2 (Fig. 2C).


Flexibility and extracellular opening determine the interaction between ligands and insect sulfakinin receptors.

Yu N, Zotti MJ, Scheys F, Braz AS, Penna PH, Nachman RJ, Smagghe G - Sci Rep (2015)

Surface, ribbon, flexibility and interaction diagrams generated by normal mode analysis of TcSKR1 (A,C,E,G) and TcSKR2 (B,D,F,H) with nonsulfated sulfakinin (nsSK) peptide docked (colored by atom type). Cavities are colored by depth from blue (shallow) to orange (deep) in TcSKR1 (A) and TcSKR2 (B). The flexibility for each amino in SKR1 and SKR2 was retrieved from normal model analysis and the root-mean-square fluctuation (RMSF) was plotted onto each structure and colored from dark blue (rigid) to red (highly flexible) (E,F). The picture demonstrates a deep cavity in both structures but with an extended opening out cavity in SKR1 (C). The red arrows (F) indicate the most significant region responsible for reduction in outer openings of SKR2 cavity (D). The top view of TcSKR2 (D,F) displays a rigid core that restricts a larger outer opening of the cavity, which to some extend hinders a deeper intrusion of peptides into cavity. The figure C shows the larger outer opening of SKR1 allows the peptides to go deeper into cavity (see lupe detail). Docking of nsSK to TcSKR1 (C) and TcSKR2 (F). The clips show the binding of nsSK in both receptors through several hydrogen bonds colored by pink dashed lines. The residues are indicated by names and colored as light cyan.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4542541&req=5

f2: Surface, ribbon, flexibility and interaction diagrams generated by normal mode analysis of TcSKR1 (A,C,E,G) and TcSKR2 (B,D,F,H) with nonsulfated sulfakinin (nsSK) peptide docked (colored by atom type). Cavities are colored by depth from blue (shallow) to orange (deep) in TcSKR1 (A) and TcSKR2 (B). The flexibility for each amino in SKR1 and SKR2 was retrieved from normal model analysis and the root-mean-square fluctuation (RMSF) was plotted onto each structure and colored from dark blue (rigid) to red (highly flexible) (E,F). The picture demonstrates a deep cavity in both structures but with an extended opening out cavity in SKR1 (C). The red arrows (F) indicate the most significant region responsible for reduction in outer openings of SKR2 cavity (D). The top view of TcSKR2 (D,F) displays a rigid core that restricts a larger outer opening of the cavity, which to some extend hinders a deeper intrusion of peptides into cavity. The figure C shows the larger outer opening of SKR1 allows the peptides to go deeper into cavity (see lupe detail). Docking of nsSK to TcSKR1 (C) and TcSKR2 (F). The clips show the binding of nsSK in both receptors through several hydrogen bonds colored by pink dashed lines. The residues are indicated by names and colored as light cyan.
Mentions: Figure 2 depicts the largest channel found in each modeled receptor that was calculated by MOLCAD. The cavities of both TcSKRs were similar in deepness from blue (shallow) to orange (deep). However, TcSKR2 had a narrow outer opening that prevented a deep intrusion of ligands into protein volume (Fig. 2D). In contrast, TcSKR1 exhibited a cavity similar in depth, but with a much larger outer opening than TcSKR2 (Fig. 2C).

Bottom Line: TcSKR1 contained a larger outer opening of the cavity than that in TcSKR2, which allows ligands a deep access into the cavity through cell membrane.Second, normal mode analysis revealed that TcSKR1 was more flexible than TcSKR2 during receptor-ligand interaction.Third, the sulfated SK (sSK) and sSK-related peptides were more potent than the nonsulfated SK, suggesting the importance of the sulfate moiety.

View Article: PubMed Central - PubMed

Affiliation: Department of Crop Protection, Faculty of Bioscience Engineering, Ghent University, 9000 Ghent, Belgium.

ABSTRACT
Despite their fundamental importance for growth, the mechanisms that regulate food intake are poorly understood. Our previous work demonstrated that insect sulfakinin (SK) signaling is involved in inhibiting feeding in an important model and pest insect, the red flour beetle Tribolium castaneum. Because the interaction of SK peptide and SK receptors (SKR) initiates the SK signaling, we have special interest on the structural factors that influence the SK-SKR interaction. First, the three-dimensional structures of the two T. castaneum SKRs (TcSKR1 and TcSKR2) were generated from molecular modeling and they displayed significance in terms of the outer opening of the cavity and protein flexibility. TcSKR1 contained a larger outer opening of the cavity than that in TcSKR2, which allows ligands a deep access into the cavity through cell membrane. Second, normal mode analysis revealed that TcSKR1 was more flexible than TcSKR2 during receptor-ligand interaction. Third, the sulfated SK (sSK) and sSK-related peptides were more potent than the nonsulfated SK, suggesting the importance of the sulfate moiety.

No MeSH data available.


Related in: MedlinePlus