Fig. 2: X-ray structures of tetrameric βI-tryptase in complex with E104.v1 Fab.

a Four Fabs simultaneously bind to tetrameric βI-tryptase, one Fab per protomer. Top Fabs bind to protomers A and C (white) and bottom Fabs bind to protomers B and D (beige); heavy (HC) and light chain (LC) are colored green and blue, respectively. b Top-down view of a showing Fabs binding to protomers A and C. c The paratope residues of the HC and LC within 4 Å of βI-tryptase (white surface) are shown as sticks and colored in green and blue, respectively. The epitope on βI-tryptase is colored violet. d Residues in βI-tryptase monomer within 4 Å of the Fab are shown as sticks and colored violet. Catalytic triad residues (H57, D102, and S195) are shown as sticks and colored teal. e Structurally aligned βI-tryptase monomers (cartoon) from βII-tryptase (pink), βI-tryptase bound to 31A.v11 Fab (dark gray), and βI-tryptase bound to E104.v1 Fab (light gray) exhibit similar conformations. Epitope residues that are unique to 31A.v11 (cyan), unique to E104.v1 (magenta), or shared (yellow) are colored accordingly. Only 31A.v11 induces a conformational change in V60c (dashed blue circle) that leads to destabilization of the large interface. f βI-tryptase peptide bonds with protons in slower H-D exchange due to E104.v1 Fab binding are colored orange (affected by both v1 and v2), cyan (affected by v1 only) and red (affected by v2 only). Tryptase protomers A (or C) and B (or D) are shown in white and beige, respectively. Vernier residues V71 and F78 are shown as sticks and CDRH2 residues are shown as violet spheres. Tryptase residues Q81-L83 that are within 4 Å of CDRH2 are shown as sticks. Tryptase key contact residues Y74 and Y75 in the small interface (protomers A-B or C-D) are shown as sticks. Individual structural images were created using PyMOL v2.2 and panels combined using Adobe Illustrator v16).