1TZ5

[pNPY19-23]-hPP bound to DPC Micelles

Summary for 1TZ5

• Entry DOI: 10.2210/pdb1tz5/pdb
• Related: 1F8P 1LJV 1TZ4
• Descriptor: Pancreatic prohormone,neuropeptide Y,Pancreatic prohormone (1 entity in total)
• Functional Keywords: npy-pp chimera, hormone-growth factor complex, hormone/growth factor
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 1
• Total formula weight: 4277.89

Authors

Lerch, M.,Kamimori, H.,Folkers, G.,Aguilar, M.I.,Beck-Sickinger, A.G.,Zerbe, O. (deposition date: 2004-07-09, release date: 2005-07-05, Last modification date: 2020-01-01)

Primary citation

Lerch, M.,Kamimori, H.,Folkers, G.,Aguilar, M.I.,Beck-Sickinger, A.G.,Zerbe, O.
Strongly Altered Receptor Binding Properties in PP and NPY Chimeras Are Accompanied by Changes in Structure and Membrane Binding
Biochemistry, 44:9255-9264, 2005

PubMed Abstract: 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.

PubMed: 15966750
DOI: 10.1021/bi0501232

Experimental method

SOLUTION NMR