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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

Cartoon diagram of Tribolium castaneum sulfakinin receptor 1 (TcSKR1) and T. castaneum sulfakinin receptor 2 (TcSKR2).The seven transmembrane α-helices building the three-dimensional fold of the proteins are differently colored from blue (N-terminus) to red (C-terminus) (upper and lower on the left) by secondary structure (upper and lower in the middle) and with extracellular loops (ECL) colored differently (upper and lower on the right). The ECL 1 is colored in orange, ECL 2 in yellow and ECL 3 in green. The N-terminus is colored in blue while C-terminus red.
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f1: Cartoon diagram of Tribolium castaneum sulfakinin receptor 1 (TcSKR1) and T. castaneum sulfakinin receptor 2 (TcSKR2).The seven transmembrane α-helices building the three-dimensional fold of the proteins are differently colored from blue (N-terminus) to red (C-terminus) (upper and lower on the left) by secondary structure (upper and lower in the middle) and with extracellular loops (ECL) colored differently (upper and lower on the right). The ECL 1 is colored in orange, ECL 2 in yellow and ECL 3 in green. The N-terminus is colored in blue while C-terminus red.

Mentions: TcSKR1 and TcSKR2 both consisted of the canonical seven α-helices crossing the cell membrane as commonly found in GPCRs (Fig. 1). Both TcSKRs exhibited three extracellular loops (ECLs) with similar number of residues. Remarkably, TcSKR1 showed eight intracellular small α-helices and two β-sheets, while SKR2 had three small α-helices and also two β-sheets.


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)

Cartoon diagram of Tribolium castaneum sulfakinin receptor 1 (TcSKR1) and T. castaneum sulfakinin receptor 2 (TcSKR2).The seven transmembrane α-helices building the three-dimensional fold of the proteins are differently colored from blue (N-terminus) to red (C-terminus) (upper and lower on the left) by secondary structure (upper and lower in the middle) and with extracellular loops (ECL) colored differently (upper and lower on the right). The ECL 1 is colored in orange, ECL 2 in yellow and ECL 3 in green. The N-terminus is colored in blue while C-terminus red.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f1: Cartoon diagram of Tribolium castaneum sulfakinin receptor 1 (TcSKR1) and T. castaneum sulfakinin receptor 2 (TcSKR2).The seven transmembrane α-helices building the three-dimensional fold of the proteins are differently colored from blue (N-terminus) to red (C-terminus) (upper and lower on the left) by secondary structure (upper and lower in the middle) and with extracellular loops (ECL) colored differently (upper and lower on the right). The ECL 1 is colored in orange, ECL 2 in yellow and ECL 3 in green. The N-terminus is colored in blue while C-terminus red.
Mentions: TcSKR1 and TcSKR2 both consisted of the canonical seven α-helices crossing the cell membrane as commonly found in GPCRs (Fig. 1). Both TcSKRs exhibited three extracellular loops (ECLs) with similar number of residues. Remarkably, TcSKR1 showed eight intracellular small α-helices and two β-sheets, while SKR2 had three small α-helices and also two β-sheets.

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