A synthetic antibody fragment targeting nicastrin affects assembly and trafficking of γ-secretase

Zhang X, Hoey R, Koide A, Dolios G, Paduch M, Nguyen P, Wu X, Li Y, Wagner SL, Wang R, Koide S, Sisodia SS

J. Biol. Chem. 2014 Dec;289(50):34851-61

PMID: 25352592


The γ-secretase complex, composed of presenilin, nicastrin (NCT), anterior pharynx-defective 1 (APH-1), and presenilin enhancer 2 (PEN-2), is assembled in a highly regulated …

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Visualization of arrestin recruitment by a G-protein-coupled receptor

Shukla AK, Westfield GH, Xiao K, Reis RI, Huang LY, Tripathi-Shukla P, Qian J, Li S, Blanc A, Oleskie AN, Dosey AM, Su M, Liang CR, Gu LL, Shan JM, Chen X, Hanna R, Choi M, Yao XJ, Klink BU, Kahsai AW, Sidhu SS, Koide S, Penczek PA, Kossiakoff AA, Woods VL, Kobilka BK, Skiniotis …

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Probing the functions of the paramyxovirus glycoproteins F and HN with a panel of synthetic antibodies

Welch BD, Paduch M, Leser GP, Bergman Z, Kors CA, Paterson RG, Jardetzky TS, Kossiakoff AA, Lamb RA

J. Virol. 2014 Oct;88(20):11713-25

PMID: 25122782


Paramyxoviruses are enveloped negative-strand RNA viruses that are significant human and animal pathogens. Most paramyxoviruses infect host cells via the concerted action of a tetrameric attachment protein (variously called HN, …

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Human-chromatin-related protein interactions identify a demethylase complex required for chromosome segregation

Marcon E, Ni Z, Pu S, Turinsky AL, Trimble SS, Olsen JB, Silverman-Gavrila R, Silverman-Gavrila L, Phanse S, Guo H, Zhong G, Guo X, Young P, Bailey S, Roudeva D, Zhao D, Hewel J, Li J, Gräslund S, Paduch M, Kossiakoff AA, Lupien M, Emili A, Wodak SJ, Greenblatt J

Cell Rep 2014 Jul;8(1):297-310


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Structural mechanism of voltage-dependent gating in an isolated voltage-sensing domain

Li Q, Wanderling S, Paduch M, Medovoy D, Singharoy A, McGreevy R, Villalba-Galea CA, Hulse RE, Roux B, Schulten K, Kossiakoff A, Perozo E

Nat. Struct. Mol. Biol. 2014 Mar;21(3):244-52

PMID: 24487958


The transduction of transmembrane electric fields into protein motion has an essential role in the generation and propagation of cellular signals. Voltage-sensing …

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New Tricks for an Old Dimer

Wells JA, Kossiakoff AA

Cell Biology, Volume 344, Issue 6185, pp. 703-704


Much of multicellular biology depends on communication through extracellular signaling molecules that bind to membrane receptors and trigger intracellular signaling events and cell behaviors. One of the first paradigm systems for understanding how polypeptide hormones bind and activate their receptors was …

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Structure of active β-arrestin-1 bound to a G-protein-coupled receptor phosphopeptide

Shukla AK, Manglik A, Kruse AC, Xiao K, Reis RI, Tseng WC, Staus DP, Hilger D, Uysal S, Huang LY, Paduch M, Tripathi-Shukla P, Koide A, Koide S, Weis WI, Kossiakoff AA, Kobilka BK, Lefkowitz RJ

Nature 2013 May;497(7447):137-41

PMID: 23604254


The functions of G-protein-coupled receptors (GPCRs) are primarily mediated and modulated by three …

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Generating conformation-specific synthetic antibodies to trap proteins in selected functional states

Paduch M, Koide A, Uysal S, Rizk SS, Koide S, Kossiakoff AA

Methods 2013 Mar;60(1):3-14

PMID: 23280336


A set of phage display sorting strategies and validation methodologies are presented that are capable of producing high performance synthetic antibodies (sABs) with customized properties. Exquisite control of antigen and conditions during the phage display selection process …

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Substance P derivatives as versatile tools for specific delivery of various types of biomolecular cargo

Rizk SS, Misiura A, Paduch M, Kossiakoff AA

Bioconjug. Chem. 2012 Jan;23(1):42-6

PMID: 22175275


The use of proteins or nucleic acids as therapeutic agents has been severely hampered by their intrinsic inability to cross the cell membrane. Moreover, common techniques for driving the delivery of macromolecules lack the ability to distinguish between healthy and …

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Mechanism of activation gating in the full-length KcsA K+ channel

Uysal S, Cuello LG, Cortes DM, Koide S, Kossiakoff AA, Perozo E

Proc. Natl. Acad. Sci. U.S.A. 2011 Jul;108(29):11896-9

PMID: 21730186


Using a constitutively active channel mutant, we solved the structure of full-length KcsA in the open conformation at 3.9 Å. The structure reveals that the activation gate expands about 20 Å, exerting a strain on …

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