NDLI: Evolutionarily Conserved Residues at Glucagon-like Peptide-1 (GLP-1) Receptor Core Confer Ligand-induced Receptor Activation

Content Provider	Journal of Biological Chemistry (JBC)
Author	Moon, Mi Jin Kim, Hee Young Park, Sumi Kim, Dong-Kyu Cho, Eun Bee Park, Cho Rong You, Dong-Joo Hwang, Jong-Ik Kim, Kyungjin Choe, Han Seong, Jae Young
Abstract	Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) play important roles in insulin secretion through their receptors, GLP1R and GIPR. Although GLP-1 and GIP are attractive candidates for treatment of type 2 diabetes and obesity, little is known regarding the molecular interaction of these peptides with the heptahelical core domain of their receptors. These core domains are important not only for specific ligand binding but also for ligand-induced receptor activation. Here, using chimeric and point-mutated GLP1R/GIPR, we determined that evolutionarily conserved amino acid residues such as Ile196 at transmembrane helix 2, Leu232 and Met233 at extracellular loop 1, and Asn302 at extracellular loop 2 of GLP1R are responsible for interaction with ligand and receptor activation. Application of chimeric GLP-1/GIP peptides together with molecular modeling suggests that His1 of GLP-1 interacts with Asn302 of GLP1R and that Thr7 of GLP-1 has close contact with a binding pocket formed by Ile196, Leu232, and Met233 of GLP1R. This study may provide critical clues for the development of peptide and/or nonpeptide agonists acting at GLP1R.
Related Links	http://www.jbc.org/content/287/6/3873.abstract
Ending Page	3884
Starting Page	3873
Page Count	12
File Format	HTM / HTML PDF
ISSN	00219258
Journal	Journal of Biological Chemistry (JBC)
Issue Number	6
Volume Number	287
DOI	10.1074/jbc.M111.276808
e-ISSN	1083351X
Language	English
Publisher	American Society for Biochemistry and Molecular Biology
Publisher Date	2012-02-03
Access Restriction	Open
Subject Keyword	G Protein-coupled Receptors (GPCR) Hormone Receptors Peptide Hormones Peptide Interactions Signal Transduction GIP GLP-1 Ligand-Receptor Interaction Receptor Activation Protein Structure and Folding
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Ligand Binding Pocket Formed by Evolutionarily Conserved Residues in the Glucagon-like Peptide-1 (GLP-1) Receptor Core Domain

Second Extracellular Loop of Human Glucagon-like Peptide-1 Receptor (GLP-1R) Has a Critical Role in GLP-1 Peptide Binding and Receptor Activation

Evolutionarily Conserved Residues at Glucagon-like Peptide-1 (GLP-1) Receptor Core Confer Ligand-induced Receptor Activation*

Second Extracellular Loop of Human Glucagon-like Peptide-1 Receptor (GLP-1R) Differentially Regulates Orthosteric but Not Allosteric Agonist Binding and Function

A Small Molecule Ligand of the Glucagon-like Peptide 1 Receptor Targets Its Amino-terminal Hormone Binding Domain

Spatial Approximations between Residues 6 and 12 in the Amino-terminal Region of Glucagon-like Peptide 1 and Its Receptor A REGION CRITICAL FOR BIOLOGICAL ACTIVITY

Functional Differences of Invariant and Highly Conserved Residues in the Extracellular Domain of the Glycoprotein Hormone Receptors

Two distinct domains of the glucagon-like peptide-1 receptor control peptide-mediated biased agonism

Ligand binding pocket formed by evolutionarily conserved residues in the glucagon-like peptide-1 (GLP-1) receptor core domain.

Evolutionarily Conserved Residues at Glucagon-like Peptide-1 (GLP-1) Receptor Core Confer Ligand-induced Receptor Activation

Similar Documents

Ligand Binding Pocket Formed by Evolutionarily Conserved Residues in the Glucagon-like Peptide-1 (GLP-1) Receptor Core Domain

Second Extracellular Loop of Human Glucagon-like Peptide-1 Receptor (GLP-1R) Has a Critical Role in GLP-1 Peptide Binding and Receptor Activation

Evolutionarily Conserved Residues at Glucagon-like Peptide-1 (GLP-1) Receptor Core Confer Ligand-induced Receptor Activation*

Second Extracellular Loop of Human Glucagon-like Peptide-1 Receptor (GLP-1R) Differentially Regulates Orthosteric but Not Allosteric Agonist Binding and Function

A Small Molecule Ligand of the Glucagon-like Peptide 1 Receptor Targets Its Amino-terminal Hormone Binding Domain

Spatial Approximations between Residues 6 and 12 in the Amino-terminal Region of Glucagon-like Peptide 1 and Its Receptor A REGION CRITICAL FOR BIOLOGICAL ACTIVITY

Functional Differences of Invariant and Highly Conserved Residues in the Extracellular Domain of the Glycoprotein Hormone Receptors

Two distinct domains of the glucagon-like peptide-1 receptor control peptide-mediated biased agonism

Ligand binding pocket formed by evolutionarily conserved residues in the glucagon-like peptide-1 (GLP-1) receptor core domain.

Evolutionarily Conserved Residues at Glucagon-like Peptide-1 (GLP-1) Receptor Core Confer Ligand-induced Receptor Activation