Apr 27 2018
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 …
Jan 10 2018
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 …
Apr 03 2017
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 …
Mar 03 2017
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, …
Mar 01 2017
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 …
Feb 26 2017
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 …
Nov 01 2016
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 …
Oct 09 2016
Shao Y, Huang H, Qin D, Li NS, Koide A, Staley JP, Koide S, Kossiakoff AA, Piccirilli JA
J. Mol. Biol. 2016 10;428(20):4100-4114
PMID: 27593161
Abstract
Antibodies that bind RNA represent an unrealized source of reagents for synthetic biology and for characterizing cellular transcriptomes. However, facile access to RNA-binding antibodies requires the engineering of effective …
Mar 09 2016
Schaefer ZP, Bailey LJ, Kossiakoff AA
Protein Sci. 2016 07;25(7):1290-8
PMID: 27334407
Abstract
Engineering monovalent Fab fragments into bivalent formats like IgGs or F(ab’)2 can lead to aggregation presumably because of nonspecific off-target interactions that induce aggregation. In an effort to further understand the molecular determinants of nonspecific interactions for engineered antibodies and natively folded …
Feb 02 2016
Dominik PK, Borowska MT, Dalmas O, Kim SS, Perozo E, Keenan RJ, Kossiakoff AA
Structure 2016 Feb;24(2):300-9
PMID: 26749445
Abstract
A major challenge in membrane biophysics is to define the mechanistic linkages between a protein’s conformational transitions and its function. We describe a novel approach to stabilize transient functional states of membrane proteins in native-like …