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2dco

From Proteopedia

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[[Image:2dco.gif|left|200px]]
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{{STRUCTURE_2dco| PDB=2dco | SCENE= }}
{{STRUCTURE_2dco| PDB=2dco | SCENE= }}
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'''S1P4 First Extracellular Loop Peptidomimetic'''
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===S1P4 First Extracellular Loop Peptidomimetic===
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==Overview==
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G protein-coupled receptors (GPCRs) control fundamental aspects of human physiology and behaviors. Knowledge of their structures, especially for the loop regions, is limited and has principally been obtained from homology models, mutagenesis data, low resolution structural studies, and high resolution studies of peptide models of receptor segments. We developed an alternate methodology for structurally characterizing GPCR loops, using the human S1P(4) first extracellular loop (E1) as a model system. This methodology uses computational peptide designs based on transmembrane domain (TM) model structures in combination with CD and NMR spectroscopy. The characterized peptides contain segments that mimic the self-assembling extracellular ends of TM 2 and TM 3 separated by E1, including residues R3.28(121) and E3.29(122) that are required for sphingosine 1-phosphate (S1P) binding and receptor activation in the S1P(4) receptor. The S1P(4) loop mimetic peptide interacted specifically with an S1P headgroup analog, O-phosphoethanolamine (PEA), as evidenced by PEA-induced perturbation of disulfide cross-linked coiled-coil first extracellular loop mimetic (CCE1a) (1)H and (15)N backbone amide chemical shifts. CCE1a was capable of weakly binding PEA near biologically relevant residues R29 and E30, which correspond to R3.28 and E3.29 in the full-length S1P(4) receptor, confirming that it has adopted a biologically relevant conformation. We propose that the combination of coiled-coil TM replacement and conformational stabilization with an interhelical disulfide bond is a general design strategy that promotes native-like structure for loops derived from GPCRs.
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(as it appears on PubMed at http://www.pubmed.gov), where 17443712 is the PubMed ID number.
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{{ABSTRACT_PUBMED_17443712}}
==About this Structure==
==About this Structure==
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2DCO is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2DCO OCA].
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2DCO is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2DCO OCA].
==Reference==
==Reference==
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[[Category: Disulfide]]
[[Category: Disulfide]]
[[Category: Helix-turn-helix]]
[[Category: Helix-turn-helix]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 00:10:55 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 10:52:00 2008''

Revision as of 07:52, 28 July 2008

Image:2dco.png

Template:STRUCTURE 2dco

S1P4 First Extracellular Loop Peptidomimetic

Template:ABSTRACT PUBMED 17443712

About this Structure

2DCO is a Single protein structure of sequence from Homo sapiens. Full experimental information is available from OCA.

Reference

Peptide design and structural characterization of a GPCR loop mimetic., Pham TC, Kriwacki RW, Parrill AL, Biopolymers. 2007 Jul;86(4):298-310. PMID:17443712

Page seeded by OCA on Mon Jul 28 10:52:00 2008

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