TY  - JOUR
A1  - Wolff, Martin
A1  - Gast, Klaus
A1  - Evers, Andreas
A1  - Kurz, Michael
A1  - Pfeiffer-Marek, Stefania
A1  - Schüler, Anja
A1  - Seckler, Robert
A1  - Thalhammer, Anja
T1  - A Conserved Hydrophobic Moiety and Helix-Helix Interactions Drive the Self-Assembly of the Incretin Analog Exendin-4
JF  - Biomolecules
N2  - 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.
KW  - biophysics
KW  - diabetes
KW  - peptides
KW  - oligomerization
KW  - conformational change
KW  - molecular modeling
KW  - static and dynamic light scattering
KW  - spectroscopy
Y1  - 2021
U6  - https://doi.org/10.3390/biom11091305
SN  - 2218-273X
VL  - 11
IS  - 9
PB  - MDPI
CY  - Basel
ER  - 
TY  - JOUR
A1  - Peng, Lei
A1  - Utesch, Tillmann
A1  - Yarman, Aysu
A1  - Jeoung, Jae-Hun
A1  - Steinborn, Silke
A1  - Dobbek, Holger
A1  - Mroginski, Maria Andrea
A1  - Tanne, Johannes
A1  - Wollenberger, Ursula
A1  - Scheller, Frieder W.
T1  - Surface-Tuned Electron Transfer and Electrocatalysis of Hexameric Tyrosine-Coordinated Heme Protein
JF  - Chemistry - a European journal
N2  - Molecular modeling, electrochemical methods, and quartz crystal microbalance were used to characterize immobilized hexameric tyrosine-coordinated heme protein (HTHP) on bare carbon or on gold electrodes modified with positively and negatively charged self-assembled monolayers (SAMs), respectively. HTHP binds to the positively charged surface but no direct electron transfer (DET) is found due to the long distance of the active sites from the electrode surfaces. At carboxyl-terminated surfaces, the neutrally charged bottom of HTHP can bind to the SAM. For this "disc" orientation all six hemes are close to the electrode and their direct electron transfer should be efficient. HTHP on all negatively charged SAMs showed a quasi-reversible redox behavior with rate constant k(s) values between 0.93 and 2.86 s(-1) and apparent formal potentials E-app(0)' between -131.1 and -249.1 mV. On the MUA/MU-modified electrode, the maximum surface concentration corresponds to a complete monolayer of the hexameric HTHP in the disc orientation. HTHP electrostatically immobilized on negatively charged SAMs shows electrocatalysis of peroxide reduction and enzymatic oxidation of NADH.
KW  - electrochemistry
KW  - electron transfer
KW  - heme proteins
KW  - molecular modeling
KW  - monolayers
Y1  - 2015
U6  - https://doi.org/10.1002/chem.201405932
SN  - 0947-6539
SN  - 1521-3765
VL  - 21
IS  - 20
SP  - 7596
EP  - 7602
PB  - Wiley-VCH
CY  - Weinheim
ER  -