Author's posts
Apr 08 2011
Allosteric control of ligand-binding affinity using engineered conformation-specific effector proteins
Rizk SS, Paduch M, Heithaus JH, Duguid EM, Sandstrom A, Kossiakoff AA
Nat. Struct. Mol. Biol. 2011 Apr;18(4):437-42
PMID: 21378967
Abstract
We describe a phage display methodology for engineering synthetic antigen binders (sABs) that recognize either the apo or the ligand-bound conformation of maltose-binding protein (MBP). sABs that preferentially recognize the maltose-bound form of MBP …
Jan 08 2011
A portable RNA sequence whose recognition by a synthetic antibody facilitates structural determination
Koldobskaya Y, Duguid EM, Shechner DM, Suslov NB, Ye J, Sidhu SS, Bartel DP, Koide S, Kossiakoff AA, Piccirilli JA
Nat. Struct. Mol. Biol. 2011 Jan;18(1):100-6
PMID: 21151117
Abstract
RNA crystallization and phasing represent major bottlenecks in RNA structure determination. Seeking to exploit antibody fragments as RNA crystallization chaperones, we have used an arginine-enriched synthetic …
Nov 08 2010
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
Abstract
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 …
Mar 08 2010
Keeping signaling in check
Kossiakoff AA, Rizk S
Structure 2010 Mar;18(3):275-6
PMID: 20223207
Abstract
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. …
Jul 08 2009
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
Abstract
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 …
Jul 08 2009
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
Abstract
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 …
Jun 08 2009
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
Abstract
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 …
Apr 08 2009
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
Abstract
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 …
Feb 08 2009
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
Abstract
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 …
Feb 08 2009
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
Abstract
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 …