التفاصيل البيبلوغرافية
| العنوان: |
A Conserved Hydrophobic Moiety and Helix–Helix Interactions Drive the Self-Assembly of the Incretin Analog Exendin-4 |
| المؤلفون: |
Martin Wolff, Klaus Gast, Andreas Evers, Michael Kurz, Stefania Pfeiffer-Marek, Anja Schüler, Robert Seckler, Anja Thalhammer |
| المصدر: |
Biomolecules; Volume 11; Issue 9; Pages: 1305 |
| بيانات النشر: |
Multidisciplinary Digital Publishing Institute |
| سنة النشر: |
2021 |
| المجموعة: |
MDPI Open Access Publishing |
| مصطلحات موضوعية: |
biophysics, diabetes, peptides, oligomerization, conformational change, molecular modeling, static and dynamic light scattering, spectroscopy |
| جغرافية الموضوع: |
agris |
| الوصف: |
Exendin-4 is a pharmaceutical peptide used in the control of insulin secretion. Structural information on exendin-4 and related peptides especially on the level of quaternary structure is scarce. We present the first published association equilibria of exendin-4 directly measured by static and dynamic light scattering. We show that exendin-4 oligomerization is pH dependent and that these oligomers are of low compactness. We relate our experimental results to a structural hypothesis to describe molecular details of exendin-4 oligomers. Discussion of the validity of this hypothesis is based on NMR, circular dichroism and fluorescence spectroscopy, and light scattering data on exendin-4 and a set of exendin-4 derived peptides. The essential forces driving oligomerization of exendin-4 are helix–helix interactions and interactions of a conserved hydrophobic moiety. Our structural hypothesis suggests that key interactions of exendin-4 monomers in the experimentally supported trimer take place between a defined helical segment and a hydrophobic triangle constituted by the Phe22 residues of the three monomeric subunits. Our data rationalize that Val19 might function as an anchor in the N-terminus of the interacting helix-region and that Trp25 is partially shielded in the oligomer by C-terminal amino acids of the same monomer. Our structural hypothesis suggests that the Trp25 residues do not interact with each other, but with C-terminal Pro residues of their own monomers. |
| نوع الوثيقة: |
text |
| وصف الملف: |
application/pdf |
| اللغة: |
English |
| العلاقة: |
Molecular Biophysics; https://dx.doi.org/10.3390/biom11091305Test |
| DOI: |
10.3390/biom11091305 |
| الإتاحة: |
https://doi.org/10.3390/biom11091305Test |
| حقوق: |
https://creativecommons.org/licenses/by/4.0Test/ |
| رقم الانضمام: |
edsbas.AFAD986B |
| قاعدة البيانات: |
BASE |
