Flexibility and Extracellular Opening Determine the Interaction Between Ligands and Insect Sulfakinin Receptors

Overview

Journal Sci Rep

Specialty Science

Date 2015 Aug 13

PMID 26267367

Citations 7

Authors

Na Yu

Moises Joao Zotti

Freja Scheys

Antonio S K Braz

Pedro H C Penna

Ronald J Nachman

Guy Smagghe

Affiliations

Soon will be listed here.

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.

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