Judy Luke

Author's posts

Characterization of engineered actin binding proteins that control filament assembly and structure

Brawley CM, Uysal S, Kossiakoff AA, Rock RS

PLoS ONE 2010 Nov;5(11):e13960

PMID: 21103060


BACKGROUND: Eukaryotic cells strictly regulate the structure and assembly of their actin filament networks in response to various stimuli. The actin binding proteins that control filament assembly are therefore attractive targets for those who wish to reorganize actin filaments and …

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Keeping signaling in check

Kossiakoff AA, Rizk S

Structure 2010 Mar;18(3):275-6

PMID: 20223207


Cytokine signaling is triggered by a hormone-induced receptor aggregation process. IL-13 employs an unconventional sequence of steps for assembling its signaling complex to trigger activation and for turning it off. Both these processes involve some unusual molecular recognition features, as discussed by Lupardus et al. …

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An engineered substance P variant for receptor-mediated delivery of synthetic antibodies into tumor cells

Rizk SS, Luchniak A, Uysal S, Brawley CM, Rock RS, Kossiakoff AA

Proc. Natl. Acad. Sci. U.S.A. 2009 Jul;106(27):11011-5

PMID: 19549879


We have developed and tested a robust delivery method for the transport of proteins to the cytoplasm of mammalian cells without compromising the integrity of the cell membrane. This receptor-mediated delivery (RMD) technology …

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Role of a salt bridge in the model protein crambin explored by chemical protein synthesis: X-ray structure of a unique protein analogue, [V15A]crambin-alpha-carboxamide

Bang D, Tereshko V, Kossiakoff AA, Kent SB

Mol Biosyst 2009 Jul;5(7):750-6

PMID: 19562114


We have used total chemical synthesis to prepare [V15A]crambin-alpha-carboxamide, a unique protein analogue that eliminates a salt bridge between the delta-guanidinium of the Arg(10) side chain and the alpha-carboxylate of Asn(46) at the C-terminus of the polypeptide chain. This salt …

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Racemic crystallography of synthetic protein enantiomers used to determine the X-ray structure of plectasin by direct methods

Mandal K, Pentelute BL, Tereshko V, Thammavongsa V, Schneewind O, Kossiakoff AA, Kent SB

Protein Sci. 2009 Jun;18(6):1146-54

PMID: 19472324


We describe the use of racemic crystallography to determine the X-ray structure of the natural product plectasin, a potent antimicrobial protein recently isolated from fungus. The protein enantiomers L-plectasin and D-plectasin were prepared by …

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Crystal structure of full-length KcsA in its closed conformation

Uysal S, Vásquez V, Tereshko V, Esaki K, Fellouse FA, Sidhu SS, Koide S, Perozo E, Kossiakoff A

Proc. Natl. Acad. Sci. U.S.A. 2009 Apr;106(16):6644-9

PMID: 19346472


KcsA is a proton-activated, voltage-modulated K(+) channel that has served as the archetype pore domain in the Kv channel superfamily. Here, we have used synthetic antigen-binding fragments …

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X-ray structure of native scorpion toxin BmBKTx1 by racemic protein crystallography using direct methods

Mandal K, Pentelute BL, Tereshko V, Kossiakoff AA, Kent SB

J. Am. Chem. Soc. 2009 Feb;131(4):1362-3

PMID: 19133782


Racemic protein crystallography, enabled by total chemical synthesis, has allowed us to determine the X-ray structure of native scorpion toxin BmBKTx1; direct methods were used for phase determination. This is the first example of a protein …

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Principal determinants leading to transition state formation of a protein-protein complex, orientation trumps side-chain interactions

Horn JR, Sosnick TR, Kossiakoff AA

Proc. Natl. Acad. Sci. U.S.A. 2009 Feb;106(8):2559-64

PMID: 19196954


The binding transition state (TS) is the rate-limiting step for transient molecular interactions. This important step in the molecular recognition process, however, is largely understood only at a qualitative level. To establish a more quantitative picture of the TS …

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Understanding mechanisms governing protein-protein interactions from synthetic binding interfaces

Kossiakoff AA, Koide S

Curr. Opin. Struct. Biol. 2008 Aug;18(4):499-506

PMID: 18638552


Recent advances in methodologies and design of combinatorial library selection have enabled comprehensive characterization of sequence space for protein-protein interaction interfaces and generation of fully synthetic binding interfaces. By exhaustively introducing and quantitatively analyzing mutations in natural interfaces, new insights into their …

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Toward chaperone-assisted crystallography: protein engineering enhancement of crystal packing and X-ray phasing capabilities of a camelid single-domain antibody (VHH) scaffold

Tereshko V, Uysal S, Koide A, Margalef K, Koide S, Kossiakoff AA

Protein Sci. 2008 Jul;17(7):1175-87

PMID: 18445622


A crystallization chaperone is an auxiliary protein that binds to a target of interest, enhances and modulates crystal packing, and provides high-quality phasing information. We critically evaluated the effectiveness of a camelid single-domain antibody (V(H)H) as …

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