About the Authors

Raffi Tonikian

Contributed equally to this work with: Raffi Tonikian, Yingnan Zhang

Affiliations Terrence Donnelly Center for Cellular and Biomolecular Research, Banting and Best Department of Medical Research, University of Toronto, Toronto, Ontario, Canada , Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada

Yingnan Zhang

Contributed equally to this work with: Raffi Tonikian, Yingnan Zhang

Affiliation Department of Protein Engineering, Genentech, South San Francisco, California, United States of America

Stephen L Sazinsky

Affiliation Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America

Bridget Currell

Affiliation Department of Molecular Biology, Genentech, South San Francisco, California, United States of America

Jung-Hua Yeh

Affiliation Department of Immunology, Genentech South San Francisco, California, United States of America

Boris Reva

Affiliation Computational Biology Center, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America

Heike A Held

Affiliation Department of Protein Engineering, Genentech, South San Francisco, California, United States of America

Brent A Appleton

Affiliation Department of Protein Engineering, Genentech, South San Francisco, California, United States of America

Marie Evangelista

Affiliation Department of Molecular Biology, Genentech, South San Francisco, California, United States of America

Yan Wu

Affiliation Department of Antibody Engineering, Genentech, South San Francisco, California, United States of America

Xiaofeng Xin

Affiliations Terrence Donnelly Center for Cellular and Biomolecular Research, Banting and Best Department of Medical Research, University of Toronto, Toronto, Ontario, Canada , Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada

Andrew C Chan

Affiliation Department of Immunology, Genentech South San Francisco, California, United States of America

Somasekar Seshagiri

Affiliation Department of Molecular Biology, Genentech, South San Francisco, California, United States of America

Laurence A Lasky

Affiliation Department of Protein Engineering, Genentech, South San Francisco, California, United States of America

Chris Sander

Affiliation Computational Biology Center, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America

Charles Boone

To whom correspondence should be addressed. E-mail: sachdev.sidhu@utoronto.ca (SSS); gary.bader@utoronto.ca (GDB); charlie.boone@utoronto.ca (CB)

Affiliations Terrence Donnelly Center for Cellular and Biomolecular Research, Banting and Best Department of Medical Research, University of Toronto, Toronto, Ontario, Canada , Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada

Gary D Bader

To whom correspondence should be addressed. E-mail: sachdev.sidhu@utoronto.ca (SSS); gary.bader@utoronto.ca (GDB); charlie.boone@utoronto.ca (CB)

¤ Current address: Terrence Donnelly Center for Cellular and Biomolecular Research and Banting and Best Department of Medical Research, University of Toronto, Toronto, Ontario, Canada

Affiliations Terrence Donnelly Center for Cellular and Biomolecular Research, Banting and Best Department of Medical Research, University of Toronto, Toronto, Ontario, Canada , Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada , Computational Biology Center, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America

Sachdev S Sidhu

To whom correspondence should be addressed. E-mail: sachdev.sidhu@utoronto.ca (SSS); gary.bader@utoronto.ca (GDB); charlie.boone@utoronto.ca (CB)

¤ Current address: Terrence Donnelly Center for Cellular and Biomolecular Research and Banting and Best Department of Medical Research, University of Toronto, Toronto, Ontario, Canada

Affiliation Department of Protein Engineering, Genentech, South San Francisco, California, United States of America

Competing Interests

YZ, BC, J-HY, BAA, ME, YW, ACC, SS, LAL, and SSS are employed by Genentech.

Author Contributions

LAL, CS, CB, GDB, and SSS conceived and designed the experiments. RT and YZ performed the phage display experiments. SLS performed the Erbin point mutant experiments. J-HY and ACC conceived and performed the cell-based assays. BC and SS performed the DNA sequencing. J-HY, HAH, ME, YW, and XX provided materials and reagents. BR and GDB performed the computational analysis. BAA and SSS performed the structural analysis. RT, GDB, and SSS produced the figures and wrote the manuscript. LAL, CS, and CB revised the manuscript.