Category: publications

Rapid Discovery and Characterization of Synthetic Neutralizing Antibodies against Anthrax Edema Toxin

Farcasanu M, Wang AG, Uchański T, Bailey LJ, Yue J, Chen Z, Wu X, Kossiakoff A, Tang WJ

Biochemistry 2019 Jun;

PMID: 31243996

Abstract

Anthrax, a lethal, weaponizable disease caused by Bacillus anthracis, acts through exotoxins that are primary mediators of systemic toxicity and also targets for neutralization by passive immunotherapy. The ease of engineering …

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Structural basis for activation of SAGA histone acetyltransferase Gcn5 by partner subunit Ada2

Sun J, Paduch M, Kim SA, Kramer RM, Barrios AF, Lu V, Luke J, Usatyuk S, Kossiakoff AA, Tan S

Proc. Natl. Acad. Sci. U.S.A. 2018 Sep;

PMID: 30224453

Abstract

The Gcn5 histone acetyltransferase (HAT) subunit of the SAGA transcriptional coactivator complex catalyzes acetylation of histone H3 and H2B N-terminal tails, posttranslational modifications associated with …

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Structural basis for activation of voltage sensor domains in an ion channel TPC1

Kintzer AF, Green EM, Dominik PK, Bridges M, Armache JP, Deneka D, Kim SS, Hubbell W, Kossiakoff AA, Cheng Y, Stroud RM

Proc. Natl. Acad. Sci. U.S.A. 2018 Sep;

PMID: 30190435

Abstract

Voltage-sensing domains (VSDs) couple changes in transmembrane electrical potential to conformational changes that regulate ion conductance through a central channel. Positively charged amino …

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The structure of the C-terminal domain of the nucleoprotein from the Bundibugyo strain of the Ebola virus in complex with a pan-specific synthetic Fab

Radwańska MJ, Jaskółowski M, Davydova E, Derewenda U, Miyake T, Engel DA, Kossiakoff AA, Derewenda ZS

Acta Crystallogr D Struct Biol 2018 Jul;74(Pt 7):681-689

PMID: 29968677

Abstract

The vast majority of platforms for the detection of viral or bacterial antigens rely on immunoassays, typically ELISA or sandwich ELISA, that are contingent on the availability of …

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Cryo-EM structure of human rhodopsin bound to an inhibitory G protein

Kang Y, Kuybeda O, de Waal PW, Mukherjee S, Van Eps N, Dutka P, Zhou XE, Bartesaghi A, Erramilli S, Morizumi T, Gu X, Yin Y, Liu P, Jiang Y, Meng X, Zhao G, Melcher K, Ernst OP, Kossiakoff AA, Subramaniam S, Xu HE

Nature 2018 Jun;

PMID: 29899450

Abstract

G-protein-coupled receptors comprise the largest …

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Ensemble cryoEM elucidates the mechanism of insulin capture and degradation by human insulin degrading enzyme

Zhang Z, Liang WG, Bailey LJ, Tan YZ, Wei H, Wang A, Farcasanu M, Woods VA, McCord LA, Lee D, Shang W, Deprez-Poulain R, Deprez B, Liu DR, Koide A, Koide S, Kossiakoff AA, Li S, Carragher B, Potter CS, Tang WJ

Elife 2018 Mar;7

PMID: 29596046

Abstract

Insulin degrading enzyme (IDE) plays key roles …

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Locking the Elbow: Improved Antibody Fab Fragments as Chaperones for Structure Determination

Bailey LJ, Sheehy KM, Dominik PK, Liang WG, Rui H, Clark M, Jaskolowski M, Kim Y, Deneka D, Tang WJ, Kossiakoff AA

J. Mol. Biol. 2018 Feb;430(3):337-347

PMID: 29273204

Abstract

Antibody Fab fragments have been exploited with significant success to facilitate the structure determination of challenging macromolecules as crystallization chaperones and as molecular fiducial marks …

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Engineered synthetic antibodies as probes to quantify the energetic contributions of ligand binding to conformational changes in proteins

Mukherjee S, Griffin DH, Horn JR, Rizk SS, Nocula-Lugowska M, Malmqvist M, Kim SS, Kossiakoff AA

J. Biol. Chem. 2018 Feb;293(8):2815-2828

PMID: 29321208

Abstract

Conformational changes in proteins due to ligand binding are ubiquitous in biological processes and are integral to many biological systems. However, it is often challenging to link ligand-induced conformational changes to …

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Targeted rescue of cancer-associated IDH1 mutant activity using an engineered synthetic antibody

Rizk SS, Mukherjee S, Koide A, Koide S, Kossiakoff AA

Sci Rep 2017 Apr;7(1):556

PMID: 28373671

Abstract

We have utilized a high-diversity phage display library to engineer antibody fragments (Fabs) that can modulate the activity of the enzyme isocitrate dehydrogenase 1 (IDH1). We show that a conformation-specific Fab can reactivate an IDH1 mutant associated with …

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Generating Conformation and Complex-Specific Synthetic Antibodies

Paduch M, Kossiakoff AA

Methods Mol. Biol. 2017;1575:93-119

PMID: 28255876

Abstract

Phage display is commonly used to identify and isolate binders from large combinatorial libraries. Here we present phage selection protocols enabling generation of synthetic antibodies capable of recognizing multiprotein complexes and conformational states. The procedure describes stages of the experiment design, optimization, and screening, …

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