Engineered ultra-high affinity synthetic antibodies for SARS-CoV-2 neutralization and detection

Slezak T, Kossiakoff AA

J Mol Biol. 2021 Mar 25;doi: 10.1016/j.jmb.2021.166956.

PMID: 33775667 PMCID: PMC7997149 DOI: 10.1016/j.jmb.2021.166956

Abstract

The Covid-19 pandemic is a centenarial global catastrophe. Similar events are likely to be recurring with more frequency in the future. The inability to control the virus’ impact is caused by many factors, but the lack of a technology …

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Recognition of an α-helical hairpin in P22 large terminase by a synthetic antibody fragment

Lokareddy RK, Ko YH, Hong N, Doll SG, Paduch M, Niederweis M, Kossiakoff AA, Cingolani G

Acta Crystallogr D Struct Biol. 2020 Sep 1;76(Pt 9):876-888.

PMID: 32876063

Abstract

The genome-packaging motor of tailed bacteriophages and herpesviruses is a multisubunit protein complex formed by several copies of a large (TerL) and a small (TerS) terminase subunit. …

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Structure of human Frizzled5 by fiducial-assisted cryo-EM supports a heterodimeric mechanism of canonical Wnt signaling

Tsutsumi N, Mukherjee S, Waghray D, Janda CY, Jude KM, Miao Y, Burg JS, Aduri NG, Kossiakoff AA, Gati C, Garcia KC.

Elife. 2020 Aug 7;9:e58464.

PMID: 32762848

Abstract

Frizzleds (Fzd) are the primary receptors for Wnt morphogens, which are essential regulators of stem cell biology, yet the structural basis of Wnt signaling through Fzd remains …

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Synthetic antibodies against BRIL as universal fiducial marks for single-particle cryoEM structure determination of membrane proteins

Mukherjee S, Erramilli SK, Ammirati M, Alvarez FJD, Fennell KF, Purdy MD, Skrobek BM, Radziwon K, Coukos J, Kang Y, Dutka P, Gao X, Qiu X, Yeager M, Eric Xu H, Han S, Kossiakoff AA

Nat Commun 2020 Mar;11(1):1598

PMID: 32221310

Abstract

We propose the concept of universal fiducials based on a set of pre-made …

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Structure and mechanism of the ER-based glucosyltransferase ALG6

Bloch JS, Pesciullesi G, Boilevin J, Nosol K, Irobalieva RN, Darbre T, Aebi M, Kossiakoff AA, Reymond JL, Locher KP

Nature 2020 03;579(7799):443-447

PMID: 32103179

Abstract

In eukaryotic protein N-glycosylation, a series of glycosyltransferases catalyse the biosynthesis of a dolichylpyrophosphate-linked oligosaccharide before its transfer onto acceptor proteins. The final seven steps occur in the lumen …

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Structure and drug resistance of the Plasmodium falciparum transporter PfCRT

Kim J, Tan YZ, Wicht KJ, Erramilli SK, Dhingra SK, Okombo J, Vendome J, Hagenah LM, Giacometti SI, Warren AL, Nosol K, Roepe PD, Potter CS, Carragher B, Kossiakoff AA, Quick M, Fidock DA, Mancia F

Nature 2019 Nov;

PMID: 31776516

Abstract

The emergence and spread of drug-resistant Plasmodium falciparum impedes global efforts to control …

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Development of “Plug and Play” Fiducial Marks for Structural Studies of GPCR Signaling Complexes by Single-Particle Cryo-EM

Dutka P, Mukherjee S, Gao X, Kang Y, de Waal PW, Wang L, Zhuang Y, Melcher K, Zhang C, Xu HE, Kossiakoff AA

Structure 2019 Oct;

PMID: 31669042

Abstract

“Universal” synthetic antibody (sAB)-based fiducial marks have been generated by customized phage display selections to facilitate the rapid structure determination of G protein-coupled receptor (GPCR) signaling …

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An engineered ultra-high affinity Fab-Protein G pair enables a modular antibody platform with multifunctional capability

Slezak T, Bailey LJ, Jaskolowski M, Nahotko DA, Filippova EV, Davydova EK, Kossiakoff AA

Protein Sci. 2019 Oct;

PMID: 31622515

Abstract

Engineered recombinant antibody-based reagents are rapidly supplanting traditionally derived antibodies in many cell biological applications. A particularly powerful aspect of these engineered reagents is that other modules having myriad functions can be attached to …

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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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