Engineered protein scaffolds as next-generation therapeutics

M Gebauer, A Skerra - Annual review of pharmacology and …, 2020 - annualreviews.org
The concept of engineering robust protein scaffolds for novel binding functions emerged 20
years ago, one decade after the advent of recombinant antibody technology. Early examples …

Eg5 targeting agents: From new anti-mitotic based inhibitor discovery to cancer therapy and resistance

I Garcia-Saez, DA Skoufias - Biochemical Pharmacology, 2021 - Elsevier
Eg5, the product of Kif11 gene, also known as kinesin spindle protein, is a motor protein
involved in the proper establishment of a bipolar mitotic spindle. Eg5 is one of the 45 …

Structural basis for power stroke vs. Brownian ratchet mechanisms of motor proteins

W Hwang, M Karplus - … of the National Academy of Sciences, 2019 - National Acad Sciences
Two mechanisms have been proposed for the function of motor proteins: The power stroke
and the Brownian ratchet. The former refers to generation of a large downhill free energy …

Direct observation of intermediate states during the stepping motion of kinesin-1

H Isojima, R Iino, Y Niitani, H Noji… - Nature chemical …, 2016 - nature.com
The dimeric motor protein kinesin-1 walks along microtubules by alternatingly hydrolyzing
ATP and moving two motor domains ('heads'). Nanometer-precision single-molecule studies …

[HTML][HTML] High-resolution structures of kinesin on microtubules provide a basis for nucleotide-gated force-generation

Z Shang, K Zhou, C Xu, R Csencsits, JC Cochran… - Elife, 2014 - elifesciences.org
Microtubule-based transport by the kinesin motors, powered by ATP hydrolysis, is essential
for a wide range of vital processes in eukaryotes. We obtained insight into this process by …

Kinesin-binding–triggered conformation switching of microtubules contributes to polarized transport

T Shima, M Morikawa, J Kaneshiro, T Kambara… - Journal of Cell …, 2018 - rupress.org
Kinesin-1, the founding member of the kinesin superfamily of proteins, is known to use only
a subset of microtubules for transport in living cells. This biased use of microtubules is …

Pathogenic mutations in the kinesin-3 motor KIF1A diminish force generation and movement through allosteric mechanisms

BG Budaitis, S Jariwala, L Rao, Y Yue, D Sept… - Journal of Cell …, 2021 - rupress.org
The kinesin-3 motor KIF1A functions in neurons, where its fast and superprocessive motility
facilitates long-distance transport, but little is known about its force-generating properties …

[HTML][HTML] The mechanism of tubulin assembly into microtubules: insights from structural studies

M Knossow, V Campanacci, LA Khodja, B Gigant - Iscience, 2020 - cell.com
Microtubules are cytoskeletal components involved in pivotal eukaryotic functions such as
cell division, ciliogenesis, and intracellular trafficking. They assemble from αβ-tubulin …

A hydrodynamic instability drives protein droplet formation on microtubules to nucleate branches

SU Setru, B Gouveia, R Alfaro-Aco, JW Shaevitz… - Nature physics, 2021 - nature.com
Liquid–liquid phase separation, occurs not only in bulk liquid, but also on surfaces. In
physiology, the nature and function of condensates on cellular structures remain …

Kinetics of nucleotide-dependent structural transitions in the kinesin-1 hydrolysis cycle

KJ Mickolajczyk, NC Deffenbaugh… - Proceedings of the …, 2015 - National Acad Sciences
To dissect the kinetics of structural transitions underlying the stepping cycle of kinesin-1 at
physiological ATP, we used interferometric scattering microscopy to track the position of gold …