scholarly journals Direct NMR Detection of Bifurcated Hydrogen Bonding in the α-Helix N-Caps of Ankyrin Repeat Proteins

2015 ◽  
Vol 137 (3) ◽  
pp. 1008-1011 ◽  
Author(s):  
Matthew R. Preimesberger ◽  
Ananya Majumdar ◽  
Tural Aksel ◽  
Kevin Sforza ◽  
Thomas Lectka ◽  
...  
Keyword(s):  
Hydrogen Bonding ◽  
Ankyrin Repeat ◽  
Repeat Proteins ◽  
Ankyrin Repeat Proteins ◽  
Α Helix

scholarly journals A truncated two-α-helix F-box present in poxvirus ankyrin-repeat proteins is sufficient for binding the SCF1 ubiquitin ligase complex

2009 ◽  
Vol 90 (5) ◽  
pp. 1224-1228 ◽  
Author(s):  
Stephanie Sonnberg ◽  
Stephen B. Fleming ◽  
Andrew A. Mercer
Keyword(s):  
Ubiquitin Ligase ◽  
Large Family ◽  
Ankyrin Repeat ◽  
Repeat Proteins ◽  
Ubiquitin Ligase Complex ◽  
Ankyrin Repeat Proteins ◽  
Α Helix

Poxviruses encode a large family of ankyrin-repeat (ANK) proteins, most of which contain an F-box-like motif necessary for the interaction of the ANK proteins with SCF1 (Skp1–Cullin1–F-box) complexes. The viral motif is generally truncated compared with the three-α-helix cellular F-box. Cellular F-box α-helices 1–3 and regions C-terminal to them have been shown to contribute to Skp1 binding. We report that the poxvirus F-boxes generally contain only two α-helices, corresponding to cellular F-box α-helices 1 and 2. A third α-helix was detected in some poxvirus F-boxes, but was not predicted to interact with Skp1. All but one of the poxvirus ANK/F-box proteins examined terminated directly after the F-box, excluding any contribution by C-terminal regions to the binding of Skp1. Here we show that, despite this truncation, the F-box of a prototypical poxvirus ANK protein, containing two α-helices, is not only necessary but also sufficient for interaction with SCF1.

Designed Ankyrin Repeat Proteins as Novel Binders for Ultrasound Molecular Imaging

2021 ◽  
Author(s):  
Alexandra Kosareva ◽  
Mukesh Punjabi ◽  
Amanda Ochoa-Espinosa ◽  
Lifen Xu ◽  
Jonas V. Schaefer ◽  
...  
Keyword(s):  
Molecular Imaging ◽  
Ankyrin Repeat ◽  
Repeat Proteins ◽  
Ultrasound Molecular Imaging ◽  
Ankyrin Repeat Proteins

scholarly journals Thermostable designed ankyrin repeat proteins (DARPins) as building blocks for innovative drugs

2021 ◽  
Author(s):  
Johannes Schilling ◽  
Christian Jost ◽  
Ioana Mariuca Ilie ◽  
Joachim Schnabl ◽  
Oralea Buechi ◽  
...  
Keyword(s):  
Melting Temperature ◽  
Building Blocks ◽  
Ankyrin Repeat ◽  
Internal Repeat ◽  
Repeat Proteins ◽  
Repeat Domain ◽  
Ankyrin Repeat Proteins ◽  
Classical Immunoglobulin ◽  
Dynamics Simulations ◽  
Innovative Drugs

AbstractDesigned Ankyrin Repeat Proteins (DARPins) are a class of antibody mimetics with a high and mostly unexplored potential in drug development. They are clinically validated and thus represent a true alternative to classical immunoglobulin formats. In contrast to immunoglobulins, they are built from solenoid protein domains comprising an N-terminal capping repeat, one or more internal repeats and a C-terminal capping repeat. By using in silico analysis and a rationally guided Ala-Scan, we identified position 17 of the N-terminal capping repeat to play a key role for the overall protein thermostability. The melting temperature of a DARPin domain with a single full-consensus internal repeat was increased by about 8°C to 10°C when the original Asp17 was replaced by Leu, Val, Ile, Met, Ala or Thr, as shown by high-temperature unfolding experiments at equilibrium. We then transferred the Asp17Leu mutation to various backgrounds, including different N- and C-terminal capping repeats and clinically validated DARPin domains, such as the VEGF-binding ankyrin repeat domain of abicipar pegol. In all cases, the proteins remained monomeric and showed improvements in the thermostability of about 8°C to 16°C. Thus, the replacement of Asp17 seems to be generically applicable to this drug class. Molecular dynamics simulations show that the Asp17Leu mutation reduces electrostatic repulsion and improves van-der-Waals packing, rendering the DARPin domain less flexible and more stable. Interestingly, such a beneficial Asp17Leu mutation is present in the N-terminal caps of three of the five DARPin domains of ensovibep, a SARS-CoV-2 entry inhibitor currently in clinical development. This mutation is likely responsible, at least in part, for the very high melting temperature (>90°C) of this promising anti-Covid-19 drug. Overall, such N-terminal capping repeats with increased thermostability seem to be beneficial for the development of innovative drugs based on DARPins.

Arpp/Ankrd2, a member of the muscle ankyrin repeat proteins (MARPs), translocates from the I-band to the nucleus after muscle injury

2007 ◽  
Vol 129 (1) ◽  
pp. 55-64 ◽  
Author(s):  
Yoshiyuki Tsukamoto ◽  
Naoki Hijiya ◽  
Shinji Yano ◽  
Shigeo Yokoyama ◽  
Chisato Nakada ◽  
...  
Keyword(s):  
Muscle Injury ◽  
Ankyrin Repeat ◽  
Repeat Proteins ◽  
Ankyrin Repeat Proteins

scholarly journals Contributions of Conserved TPLH Tetrapeptides to the Conformational Stability of Ankyrin Repeat Proteins

2010 ◽  
Vol 399 (1) ◽  
pp. 168-181 ◽  
Author(s):  
Yi Guo ◽  
Chunhua Yuan ◽  
Feng Tian ◽  
Kun Huang ◽  
Christopher M. Weghorst ◽  
...  
Keyword(s):  
Conformational Stability ◽  
Ankyrin Repeat ◽  
Repeat Proteins ◽  
Ankyrin Repeat Proteins

SPRi-MALDI MS: characterization and identification of a kinase from cell lysate by specific interaction with different designed ankyrin repeat proteins

2016 ◽  
Vol 409 (7) ◽  
pp. 1827-1836 ◽  
Author(s):  
Ulrike Anders ◽  
Jonas V. Schaefer ◽  
Fatima-Ezzahra Hibti ◽  
Chiraz Frydman ◽  
Detlev Suckau ◽  
...  
Keyword(s):  
Specific Interaction ◽  
Ankyrin Repeat ◽  
Maldi Ms ◽  
Cell Lysate ◽  
Repeat Proteins ◽  
Ankyrin Repeat Proteins

scholarly journals Selection and Characterization of Her2 Binding-designed Ankyrin Repeat Proteins

2006 ◽  
Vol 281 (46) ◽  
pp. 35167-35175 ◽  
Author(s):  
Christian Zahnd ◽  
Frédéric Pecorari ◽  
Nadine Straumann ◽  
Emanuel Wyler ◽  
Andreas Plückthun
Keyword(s):  
Ankyrin Repeat ◽  
Repeat Proteins ◽  
Ankyrin Repeat Proteins

scholarly journals Conformation-Dependent Recognition of HIV gp120 by Designed Ankyrin Repeat Proteins Provides Access to Novel HIV Entry Inhibitors

2013 ◽  
Vol 87 (10) ◽  
pp. 5868-5881 ◽  
Author(s):  
A. Mann ◽  
N. Friedrich ◽  
A. Krarup ◽  
J. Weber ◽  
E. Stiegeler ◽  
...  
Keyword(s):  
Ankyrin Repeat ◽  
Entry Inhibitors ◽  
Repeat Proteins ◽  
Hiv Entry ◽  
Ankyrin Repeat Proteins ◽  
Hiv Gp120 ◽  
Hiv Entry Inhibitors
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