1tz5: Difference between revisions
New page: left|200px<br /> <applet load="1tz5" size="450" color="white" frame="true" align="right" spinBox="true" caption="1tz5" /> '''[pNPY19-23]-hPP bound to DPC Micelles'''<br... |
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[[Image:1tz5.gif|left|200px]]<br /> | [[Image:1tz5.gif|left|200px]]<br /><applet load="1tz5" size="350" color="white" frame="true" align="right" spinBox="true" | ||
<applet load="1tz5" size=" | |||
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'''[pNPY19-23]-hPP bound to DPC Micelles'''<br /> | '''[pNPY19-23]-hPP bound to DPC Micelles'''<br /> | ||
==Overview== | ==Overview== | ||
Neuropeptide Y (NPY) and the pancreatic polypeptide (PP) are members of | Neuropeptide Y (NPY) and the pancreatic polypeptide (PP) are members of the neuropeptide Y family of hormones. They bind to the Y receptors with very different affinities: Whereas PP is highly selective for the Y(4) receptor, NPY displays highest affinites for Y(1), Y(2), and Y(5) receptor subtypes. Introducing the NPY segment 19-23 into PP leads to an increase in affinity at the Y(1) and Y(2) receptor subtypes whereas the exchange of this segment from PP into NPY leads to a large decrease in affinity at all receptor subtypes. PP displays a very stable structure in solution, with the N terminus being back-folded onto the C-terminal alpha-helix (the so-called PP-fold). The helix of NPY is less stable and the N terminus is freely diffusing in solution. The exchange of this segment, however, does not alter the PP-fold propensities of the chimeric peptides in solution. The structures of the phospholipid micelle-bound peptides serving to mimic the membrane-bound species display segregation into a more flexible N-terminal region and a well-defined alpha-helical region. The introduction of the [19-23]-pNPY segment into hPP leads to an N-terminal extension of the alpha-helix, now starting at Pro(14) instead of Met(17). In contrast, a truncated helix is observed in [(19)(-)(23)hPP]-pNPY, starting at Leu(17) instead of Ala(14). All peptides display moderate binding affinities to neutral membranes (K(assoc) in the range of 1.7 to 6.8 x 10(4) mol(-)(1) as determined by surface plasmon resonance) with the differences in binding being most probably related to the exchange of Arg-19 (pNPY) by Glu-23 (hPP). Differences in receptor binding properties between the chimeras and their parental peptides are therefore most likely due to changes in the conformation of the micelle-bound peptides. | ||
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
1TZ5 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens_and_sus_scrofa Homo sapiens and sus scrofa] with NH2 as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | 1TZ5 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens_and_sus_scrofa Homo sapiens and sus scrofa] with <scene name='pdbligand=NH2:'>NH2</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1TZ5 OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens and sus scrofa]] | [[Category: Homo sapiens and sus scrofa]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Aguilar, M | [[Category: Aguilar, M I.]] | ||
[[Category: Beck-Sickinger, A | [[Category: Beck-Sickinger, A G.]] | ||
[[Category: Folkers, G.]] | [[Category: Folkers, G.]] | ||
[[Category: Kamimori, H.]] | [[Category: Kamimori, H.]] | ||
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[[Category: npy-pp chimera]] | [[Category: npy-pp chimera]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:18:52 2008'' | ||
Revision as of 16:18, 21 February 2008
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[pNPY19-23]-hPP bound to DPC Micelles
OverviewOverview
Neuropeptide Y (NPY) and the pancreatic polypeptide (PP) are members of the neuropeptide Y family of hormones. They bind to the Y receptors with very different affinities: Whereas PP is highly selective for the Y(4) receptor, NPY displays highest affinites for Y(1), Y(2), and Y(5) receptor subtypes. Introducing the NPY segment 19-23 into PP leads to an increase in affinity at the Y(1) and Y(2) receptor subtypes whereas the exchange of this segment from PP into NPY leads to a large decrease in affinity at all receptor subtypes. PP displays a very stable structure in solution, with the N terminus being back-folded onto the C-terminal alpha-helix (the so-called PP-fold). The helix of NPY is less stable and the N terminus is freely diffusing in solution. The exchange of this segment, however, does not alter the PP-fold propensities of the chimeric peptides in solution. The structures of the phospholipid micelle-bound peptides serving to mimic the membrane-bound species display segregation into a more flexible N-terminal region and a well-defined alpha-helical region. The introduction of the [19-23]-pNPY segment into hPP leads to an N-terminal extension of the alpha-helix, now starting at Pro(14) instead of Met(17). In contrast, a truncated helix is observed in [(19)(-)(23)hPP]-pNPY, starting at Leu(17) instead of Ala(14). All peptides display moderate binding affinities to neutral membranes (K(assoc) in the range of 1.7 to 6.8 x 10(4) mol(-)(1) as determined by surface plasmon resonance) with the differences in binding being most probably related to the exchange of Arg-19 (pNPY) by Glu-23 (hPP). Differences in receptor binding properties between the chimeras and their parental peptides are therefore most likely due to changes in the conformation of the micelle-bound peptides.
DiseaseDisease
Known disease associated with this structure: Neutral lipid storage disease with myopathy OMIM:[609059]
About this StructureAbout this Structure
1TZ5 is a Single protein structure of sequence from Homo sapiens and sus scrofa with as ligand. Full crystallographic information is available from OCA.
ReferenceReference
Strongly altered receptor binding properties in PP and NPY chimeras are accompanied by changes in structure and membrane binding., Lerch M, Kamimori H, Folkers G, Aguilar MI, Beck-Sickinger AG, Zerbe O, Biochemistry. 2005 Jun 28;44(25):9255-64. PMID:15966750
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