Nature Communications (Dec 2020)
Bivalent antibody pliers inhibit β-tryptase by an allosteric mechanism dependent on the IgG hinge
- Henry R. Maun,
- Rajesh Vij,
- Benjamin T. Walters,
- Ashley Morando,
- Janet K. Jackman,
- Ping Wu,
- Alberto Estevez,
- Xiaocheng Chen,
- Yvonne Franke,
- Michael T. Lipari,
- Mark S. Dennis,
- Daniel Kirchhofer,
- Claudio Ciferri,
- Kelly M. Loyet,
- Tangsheng Yi,
- Charles Eigenbrot,
- Robert A. Lazarus,
- James T. Koerber
Affiliations
- Henry R. Maun
- Department of Early Discovery Biochemistry, Genentech, Inc.
- Rajesh Vij
- Department of Antibody Engineering, Genentech, Inc.
- Benjamin T. Walters
- Department of Biochemical and Cellular Pharmacology, Genentech, Inc.
- Ashley Morando
- Department of Biochemical and Cellular Pharmacology, Genentech, Inc.
- Janet K. Jackman
- Department of Immunology Discovery, Genentech, Inc.
- Ping Wu
- Department of Structural Biology, Genentech, Inc.
- Alberto Estevez
- Department of Structural Biology, Genentech, Inc.
- Xiaocheng Chen
- Department of Antibody Engineering, Genentech, Inc.
- Yvonne Franke
- Department of Biomolecular Resources, Genentech, Inc.
- Michael T. Lipari
- Department of Early Discovery Biochemistry, Genentech, Inc.
- Mark S. Dennis
- Department of Antibody Engineering, Genentech, Inc.
- Daniel Kirchhofer
- Department of Early Discovery Biochemistry, Genentech, Inc.
- Claudio Ciferri
- Department of Structural Biology, Genentech, Inc.
- Kelly M. Loyet
- Department of Biochemical and Cellular Pharmacology, Genentech, Inc.
- Tangsheng Yi
- Department of Immunology Discovery, Genentech, Inc.
- Charles Eigenbrot
- Department of Structural Biology, Genentech, Inc.
- Robert A. Lazarus
- Department of Early Discovery Biochemistry, Genentech, Inc.
- James T. Koerber
- Department of Antibody Engineering, Genentech, Inc.
- DOI
- https://doi.org/10.1038/s41467-020-20143-x
- Journal volume & issue
-
Vol. 11,
no. 1
pp. 1 – 12
Abstract
β-tryptases are responsible for most of the proteolytic activity during mast cell activation. Here, the authors develop β-tryptase-inhibiting antibodies and provide structural and biochemical evidence that the bivalency of the antibodies is a prerequisite for their inhibitory activity.
