Category: publications

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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Prolactin Receptor-Mediated Internalization of Imaging Agents Detects Epithelial Ovarian Cancer with Enhanced Sensitivity and Specificity

Sundaram KM, Zhang Y, Mitra AK, Kouadio JK, Gwin K, Kossiakoff AA, Roman BB, Lengyel E, Piccirilli JA

Cancer Res. 2017 Apr;77(7):1684-1696

PMID: 28202518

Abstract

Poor prognosis of ovarian cancer, the deadliest of the gynecologic malignancies, reflects major limitations associated with detection and diagnosis. Current methods lack high sensitivity to detect small tumors and high …

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Generation of Synthetic Antibody Fragments to Detergent Solubilized Membrane Proteins

Uysal S, Kossiakoff AA

Springer Protocols Handbook, p1-13

Abstract

Structural determination of membrane proteins is extremely challenging due to the physical characteristics of membrane proteins themselves and the lack of adequate tools and technologies to perform the studies. Recent developments in micro-focus X-ray beams, novel detergents, protein thermo-stabilization, and protein engineering have been essential in …

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The Preserved HTH-Docking Cleft of HIV-1 Integrase Is Functionally Critical

Galilee M, Britan-Rosich E, Griner SL, Uysal S, Baumgärtel V, Lamb DC, Kossiakoff AA, Kotler M, Stroud RM, Marx A, Alian A

Structure 2016 11;24(11):1936-1946

PMID: 27692964

Abstract

HIV-1 integrase (IN) catalyzes viral DNA integration into the host genome and facilitates multifunctional steps including virus particle maturation. Competency of IN to form multimeric assemblies is …

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