The Furman Lab

Dan Reshef, Computational Biologist

Evogene Ltd.



Lab Project:

The cohesin module: evolution of domain repeats and affinity and specificity in the cohesin-dockerin interaction

Project description

I conducted a large-scale study of protein domain repeats, starting with the cohesin modules on the scaffold protein of the cellulosome. We have discovered that protein domain repeats are more conserved in prokaryotes than in eukaryotes. The limiting step of the creation of multiple repeats is the two-repeat state. Two repeats (only) tend to greatly differ one from another. However, once a protein reaches a higher number of repeats, conservation can be higher. I also studied the conservation of protein domains when it is found with different neighboring domains.

The cellulosome is a multi-protein complex used by bacteria for the degradation of cellulose. The content of the complex is dictated by multiple interactions between cohesin and dockerin domains. These are of high affinity and remarkable specificity: cross-species cohesin and dockerins do usually not bind, indicating the evolutionary pressure on the interaction. I studied the structural factors that enable the high affinity and restrict the specificity of the interaction. My goal was to use this knowledge to design a switch, i.e. to create a new exclusive dockerin-cohesin pair. We used Rosetta for modeling of the structure and binding energy of protein complexes.

Education
  • 2012-present. Employed at Evogene
  • 2007-2012 Ph.D., The Hebrew University of Jerusalem, the Institute for Medical Research, Department of Microbiology and Molecular Genetics. Thesis: The cohesin domain: the type-I cohesin-dockerin interaction and a model for domain conservation and evolution. Advisor: Prof. Ora Schueler-Furman.
  • 2003-2006 M.Sc., Ben-Gurion University of the Negev, Department of Life Sciences. Thesis: Identifying Functional Sites in Enzyme Structures using Energy Functions. Advisor: Dr. Chen Keasar. With honors.
  • 1997, 2001-2003 B.Sc., Ben Gurion University of the Negev, Department of Life Sciences.
Publications
  • Slutzki M, Reshef D, Barak Y, Haimovitz R, Rotem-Bamberger S, Lamed R, Bayer EA, Schueler-Furman O. Crucial roles of single residues in binding affinity, specificity and promiscuity in the cellulosomal cohesin-dockerin interface. (2015) JBC PMID: 25833947.
  • Slutzki M, Barak Y, Reshef D, Schueler-Furman O, Lamed R, Bayer EA. Measurements of relative binding of cohesin and dockerin mutants using an advanced ELISA technique for high-affinity interactions. (2012) Methods Enzymol. 510:417-28.
  • Yahalom R, Reshef D, Wiener A, Frankel S, Kalisman N, Lerner B, Keasar C. Structure-based identification of catalytic residues. (2011) Proteins. 79:1952-63.
  • Reshef D, Itzhaki Z, Schueler-Furman O. Increased sequence conservation of domain repeats in prokaryotic proteins. (2010) Trends Genet. 26:383-7.
  • Ben-nun-Shaul O, Bronfeld H, Reshef D, Schueler-Furman O, Oppenheim A. The SV40 capsid is stabilized by a conserved pentapeptide hinge of the major capsid protein VP1. (2009) J Mol Biol. 386:1382-91.
  • Bakhrat A, Baranes-Bachar K, Reshef D, Voloshin O, Krichevsky O, Raveh D. Nuclear export of Ho endonuclease of yeast via Msn5. (2008) Curr Genet. 54:271-81.
  • Kalisman N, Levi A, Maximova T, Reshef D, Zafriri-Lynn S, Gleyzer Y, Keasar C. MESHI: a new library of Java classes for molecular modeling. (2005) Bioinformatics. 21:3931-2.
Presentations at Meetings
  • Reshef D, Carmel L, Schueler-Furman O. Context-dependent conservation of protein domains. (2012). GSI, Beer-Sheva, Israel. Oral presentation.
  • Reshef D, Carmel L, Schueler-Furman O. Context-dependent conservation of protein domains. (2012). SMBE, Dublin, Ireland. Poster.
  • Reshef D, Carmel L, Schueler-Furman O. Context-dependent conservation of protein domains. (2012). IBS, Jerusalem, Israel. Poster.
  • Reshef D, Itzhaki Z, Schueler-Furman O. Enrichment of highly-conserved domain repeats in prokaryotic proteins. (2010). IMRIC conference, Eilat, Israel. Poster.
  • Reshef D, Bayer EA, Schueler-Furman O. Conservation of domain repeats in cellulosome scaffoldins and other proteins. (2009). GRC conference on cellulosomes, cellulases & other carbohydrate modifying enzymes. Andover, NH, USA. Poster.
  • Reshef D, Slutzki M, Haimovitz R, Barak Y, Lamed R, Bayer EA, Schueler-Furman O. Crossing the (specificity) barrier: Single-mutation cohesin specificity switch from C. thermicellum to C. cellulolyticum dockerin. (2009). GRC conference on cellulosomes, cellulases & other carbohydrate modifying enzymes. Andover, NH, USA. Poster.
  • Slutzki M, Reshef D, Haimovitz R, Barak Y, Lamed R, Bayer EA, Schueler-Furman O. Determinants of affinity and specificity in the C. thermocellum type-I cohesin-dockerin interaction. (2009). GRC conference on cellulosomes, cellulases & other carbohydrate modifying enzymes. Andover, NH, USA. Poster.
  • Reshef D, Bayer EA, Schueler-Furman O. Conservation of domain repeats in cellulosome scaffoldins and other proteins. (2009). IBS, Rechovot, Israel. Poster.
  • Reshef D, Schueler-Furman O. Conservation of domain repeats in cellulosome scaffoldins and other proteins. (2009). Evolution in Jerusalem, Jerusalem, Israel. Poster.
  • Reshef D, Slutski M, Barak Y, Bayer EA, Schueler-Furman, O. Affinity and specificity in the cohesion-dockerin interaction. (2008). Molecular perspectives on protein-protein interactions, Dubrovnik, Croatia. Poster.
  • Reshef, D., Slutski, M. Barak, Y., Bayer, EA. and Schueler-Furman, O. Factors Governing the affinity and specificity in the cohesin-dockerin complex. (2008). Ilanit/FISEB, Eilat, Israel. Poster.
  • Yahalom, R., Reshef, D., Kalisman, N., Gleyzer, Y., Lerner, B. and Keasar, C. Identification of catalytic residues based on destabilizing properties and an SVM classifier. (2007). ISMB, Eilat, Israel. Poster.
  • Reshef D., Kalisman N., Glyezer Y. and Keasar C. (2006). Prediction of functional sites in enzyme structures using energy functions. RECOMB, Venice, Italy. Poster
  • Reshef D., Kalisman N., Glyezer Y. and Keasar C. (2005). Prediction of functional sites in protein structures using energy functions. IBS, Beer-Sheva, Israel. Poster
Contact
  • Mail: dan.reshef at mail.huji.ac.il
  • Phone (Ein-Karem): 02-6757063