Shohei Koide
Research Summary / Selected Publications
We are interested in creating new protein functions and using such designer proteins to understand and control biology. Our research is interdisciplinary, integrating approaches in directed evolution, structural biology, protein chemistry, spectroscopy and cell biology.
Protein Design. The exercise of generating novel binding proteins tests our understanding of the molecular mechanisms underlying molecular recognition and protein evolution. We aim to define the "minimalist" requirements for tight and specific interfaces (e.g. how much chemical and structural diversity is required for affinity and specificity?) by constructing small but highly functional binding proteins.
We use two classes of protein systems. The first is the "monobodies", a small beta-sandwich protein that presents surface binding loops, and synthetic antibodies, both representing a ubiquitous mode of binding seen in natural proteins. The second is the "affinity clamps", a two-domain architecture that we have created specifically for recognizing flexible peptide segments. We combine structure-guided design and directed evolution utilizing phage display technologies.
Dissecting and controlling signaling networks using designer proteins. Designer binding proteins are powerful tools that enable new types of biological investigation. We are now able to generate synthetic binding proteins that bind a target of interest tightly and exquisitely selectively. We express them in cells where they act as minimally invasive inhibitors of protein-protein interactions. Importantly, our approach does not alter the endogenous genome of the cells. We are utilizing this uniquely powerful capacity to dissect signaling networks and to control aberrant proteins responsible for human diseases. We currently focus on signaling mediated by tyrosine phosphorylation and histone modification.
We are interested in creating new protein functions and using such designer proteins to understand and control biology. Our research is interdisciplinary, integrating approaches in directed evolution, structural biology, protein chemistry, spectroscopy and cell biology.
Protein Design. The exercise of generating novel binding proteins tests our understanding of the molecular mechanisms underlying molecular recognition and protein evolution. We aim to define the "minimalist" requirements for tight and specific interfaces (e.g. how much chemical and structural diversity is required for affinity and specificity?) by constructing small but highly functional binding proteins.
We use two classes of protein systems. The first is the "monobodies", a small beta-sandwich protein that presents surface binding loops, and synthetic antibodies, both representing a ubiquitous mode of binding seen in natural proteins. The second is the "affinity clamps", a two-domain architecture that we have created specifically for recognizing flexible peptide segments. We combine structure-guided design and directed evolution utilizing phage display technologies.
Dissecting and controlling signaling networks...
Huang J, Koide A, Makabe K & Koide S (2008) Design of protein function leaps by directed domain interface evolution. Proc Natl Acad Sci U S A, 105, 6578-6583. Link
Gilbreth RN, Esaki K, Koide A, Sidhu SS & Koide S. (2008). A dominant conformational role for amino acid diversity in minimalist protein-protein interfaces. J Mol Biol, 381, 407-418. Link
Biancalana M, Makabe K, Koide A & Koide S. (2009) Molecular mechanism of thioflavin-T binding to the surface of β-rich peptide self-assemblies. J Mol Biol, 385, 1052-1063. Link
Koide S. (2009) Design and engineering of synthetic recognition interfaces using non-antibody scaffolds. in Protein Engineering and Design (Ed. Cochran J & Park S). Taylor & Francis.
Koide S (2009) Generation of novel protein functions by domain combinations and rearrangements. Curr Opin Biotechnol, 20, 398-404.
Dutta S, Koide A & Koide S. (2008) High-throughput analysis of the protein sequence-stability landscape using a quantitative "yeast surface two-hybrid" system and fragment reconstitution. J Mol Biol, 382, 721-733. Link
Ye J, Fellouse FA, Koide A, Sidhu SS, Koide S, Kossiakoff AA & Piccirilli JA (2008) Synthetic antibodies for specific recognition and crystallization of structured RNA. Proc Natl Acad Sci U S A, 105, 82-87. Link
Koide A., Gilbreth R, Esaki K, Tereshko V. & Koide S. (2007) High-affinity single-domain binding proteins with a binary code interface, Proc Natl Acad Sci U S A, 104,6632-6637. Link
Sidhu SS & Koide S. (2007). Phage display for engineering and analyzing molecular recognition interfaces. Curr Opin Struct Biol, 17, 481-487. Link
Fellouse FA, Esaki K, Birtalan S, Raptis D, Cancasci VJ, Koide A, Jhurani P, Vasser M, Wiesmann C, Kossiakoff AA, Koide S & Sidhu SS (2007) High-throughput generation of synthetic antibodies from highly functional minimalist phage-displayed libraries, J Mol Biol 373, 924–940. Link
Koide A, Tereshko V, Uysal S, Margalef K, Kossiakoff AA & Koide S (2007) Exploring the capacity of minimalist protein interfaces: interface energetics and affinity maturation to picomolar KD of a single-domain antibody with a flat paratope, J Mol Biol 373, 941–953. Link
Makabe K, McElheny D, Tereshko V, Hilyard V, Gawlak G, Yan S, Koide A & Koide S. (2006) Atomic structures of peptide self-assembly mimics. Proc Natl Acad Sci USA, 103, 17753-8. Link
Koide, A., Bailey, C. W., Huang, X. and Koide, S. (1998). "The fibronectin type III domain as a scaffold for novel binding proteins." J. Mol. Biol. 284: 1141-1151.
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Koide, S., Huang, X., Link, K., Koide, A., Bu, Z. and Engelman, D. M. (2000). "Design of single-layer beta-sheets without a hydrophobic core." Nature 403: 456-460.
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Yan, S., Kennedy, S.D. & Koide, S. (2002) Thermodynamic and Kinetic Exploration of the Energy Landscape of Borrelia OspA by Native State Hydrogen Exchange, J. Mol. Biol. 323: 363-375. Link
Huang J, Koide A, Makabe K & Koide S (2008) Design of protein function leaps by directed domain interface evolution. Proc Natl Acad Sci U S A, 105, 6578-6583. Link
Gilbreth RN, Esaki K, Koide A, Sidhu SS & Koide S. (2008). A dominant conformational role for amino acid diversity in minimalist protein-protein interfaces. J Mol Biol, 381, 407-418. Link
Biancalana M, Makabe K, Koide A & Koide S. (2009) Molecular mechanism of thioflavin-T binding to the surface of β-rich peptide self-assemblies. J Mol Biol, 385, 1052-1063. Link
Koide S. (2009) Design and engineering of synthetic recognition interfaces using non-antibody scaffolds. in Protein Engineering and Design (Ed. Cochran J & Park S). Taylor & Francis.
Koide S (2009) Generation of novel protein functions by domain combinations and rearrangements. Curr Opin Biotechnol, 20, 398-404.
