Prediction of the 3D structure of FMRF-amide neuropeptides bound to the mouse MrgC11 GPCR and experimental validation.

Prediction of the 3D structure of FMRF-amide neuropeptides bound to the mouse MrgC11 GPCR and experimental validation. Research Abstract Details 

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Prediction of the 3D structure of FMRF-amide neuropeptides bound to the mouse MrgC11 GPCR and experimental validation. Abstract Text:

Jiyoung Heo,Sang-Kyou Han,Nagarajan Vaidehi,John Wendel,Peter Kekenes-Huskey,William A Goddard,

We report the 3D structure predicted for the mouse MrgC11 (mMrgC11) receptor by using the MembStruk computational protocol, and the predicted binding site for the F-M-R-F-NH(2) neuropeptide together with four singly chirally modified ligands. We predicted that the R-F-NH(2) part of the tetrapeptide sticks down into the protein between the transmembrane (TM) domains 3, 4, 5, and 6. The Phe (F-NH(2)) interacted favorably with Tyr110 (TM3), while the Arg makes salt bridges to Asp161 (TM4) and Asp179 (TM5). We predicted that the Met extends from the binding site, but the terminal Phe residue sticks back into an aromatic/hydrophobic site flanked by Tyr237, Leu238, Leu240, and Tyr256 (TM6), and Trp162 (TM4). We carried out subsequent mutagenesis experiments followed by intracellular calcium-release assays that demonstrated the dramatic decrease in activity for the Tyr110Ala, Asp161Ala, and Asp179Ala substitutions, which was predicted by our model. These experiments provide strong evidence that our predicted G protein-coupled receptor (GPCR) structure is sufficiently accurate to identify binding sites for selective ligands. Similar studies were made with the mMrgA1 receptor, which did not bind the R-F-NH(2) dipeptide; we explain this to be due to the increased hydrophobic character of the binding pocket in mMrgA1.

Prediction of the 3D structure of FMRF-amide neuropeptides bound to the mouse MrgC11 GPCR and experimental validation. Publishing Authors By Initials

J Heo,SK Han,N Vaidehi,J Wendel,P Kekenes-Huskey,WA Goddard,

For similar proteins: membrane proteins: receptors, cell surface: receptors, g-protein-coupled research abstracts see: proteins: membrane proteins: receptors, cell surface: receptors, g-protein-coupled research

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Prediction of the 3D structure of FMRF-amide neuropeptides bound to the mouse MrgC11 GPCR and experimental validation. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Chembiochem : a European journal of chemical biolo

VOLUME: 8

Page Numbers: 1527-39

Journal Abbreviation: Chembiochem

ISSN: 1439-4227

DAY: 3

MONTH: Sep

YEAR: 2007

Prediction of the 3D structure of FMRF-amide neuropeptides bound to the mouse MrgC11 GPCR and experimental validation. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 100937360

Prediction of the 3D structure of FMRF-amide neuropeptides bound to the mouse MrgC11 GPCR and experimental validation. Keywords Mesh Terms:

KEYWORDS: Receptors, G-Protein-Coupled

MESH TERMS: metabolism

Chemical & Substance for Abstract: Prediction of the 3D structure of FMRF-amide neuropeptides bound to the mouse MrgC11 GPCR and experimental validation. Information

Substance Name: Calcium

Registry Number: 7440-70-2

Grant and Affiliation Information for Prediction of the 3D structure of FMRF-amide neuropeptides bound to the mouse MrgC11 GPCR and experimental validation.

AFFILIATION: Materials and Process Simulations Center (139-74), Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA.

Country: Germany

AGENCY: United States NINDS

GRANT: NS048499

ACRONYM: NS

MEDLINETA: Chembiochem

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