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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

Amino acid residues involved in binding of SK-related peptides in TcSKR1 (A) and TcSKR2 (B). The residues were collected for the binding of TcSKRs with sSK, nsSK, alanine-substituted and truncated SK peptides in Table 1 and Table supplement 1. The residues are represented with white single-letter codes in black filled circles. Figures were generated online with Protter v.1.0.
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f4: Amino acid residues involved in binding of SK-related peptides in TcSKR1 (A) and TcSKR2 (B). The residues were collected for the binding of TcSKRs with sSK, nsSK, alanine-substituted and truncated SK peptides in Table 1 and Table supplement 1. The residues are represented with white single-letter codes in black filled circles. Figures were generated online with Protter v.1.0.

Mentions: Figure 4 summarizes the amino acid residues involved in the binding of TcSKRs and SK-related peptides tested in Table 1. The interactive residues in receptors were found in both the extracellular region and transmembrane (TM) region in TcSKR1, while they were only located in the extracellular region in TcSKR2 (Fig. 4; supplementary table 1). For these docked peptides, with exception of S143 of TM 4, the TM regions in TcSKR2 were not involved in the ligand-receptor interaction.


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)

Amino acid residues involved in binding of SK-related peptides in TcSKR1 (A) and TcSKR2 (B). The residues were collected for the binding of TcSKRs with sSK, nsSK, alanine-substituted and truncated SK peptides in Table 1 and Table supplement 1. The residues are represented with white single-letter codes in black filled circles. Figures were generated online with Protter v.1.0.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f4: Amino acid residues involved in binding of SK-related peptides in TcSKR1 (A) and TcSKR2 (B). The residues were collected for the binding of TcSKRs with sSK, nsSK, alanine-substituted and truncated SK peptides in Table 1 and Table supplement 1. The residues are represented with white single-letter codes in black filled circles. Figures were generated online with Protter v.1.0.
Mentions: Figure 4 summarizes the amino acid residues involved in the binding of TcSKRs and SK-related peptides tested in Table 1. The interactive residues in receptors were found in both the extracellular region and transmembrane (TM) region in TcSKR1, while they were only located in the extracellular region in TcSKR2 (Fig. 4; supplementary table 1). For these docked peptides, with exception of S143 of TM 4, the TM regions in TcSKR2 were not involved in the ligand-receptor interaction.

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