Engineering the Fab fragment of the anti-IgE omalizumab to prevent Fab crystallization and permit IgE-Fc complex crystallization

Mitropoulou, A.N.; Ceska, T.; Heads, J.T.; Beavil, A.J.; Henry, A.J.; McDonnell, J.M.; Sutton, B.J.; Davies, A.M.

doi:10.1107/S2053230X20001466

Figure 5
Conformational diversity in the omalizumab CDRs. (a) In molecule FabXol1^2C (blue), the binding of a glycerol molecule (GOL) alters the position of Tyr33 (CDRH1), which adopts a similar position to that in the IgE-Fc-bound Fab (yellow; Davies et al., 2017

). The FabXol¹ structure (gray) is shown for comparison. (b) Compared with the FabXol1 structure (gray), molecule FabXol1^2C from the FabXol1² structure (blue) and FabXol3 from the complex with IgE-Fc (yellow), CDRH1 adopts a conformation in the unbound FabXol3 structure (pink) that alters the positions of Tyr27 and Ile29 (CDRH1). Phe79 also adopts a different position. By contrast, Tyr33 (CDRH1) adopts a similar position in FabXol1^2C (blue), unbound FabXol3 (pink) and FabXol3 bound to IgE-Fc (yellow). Tyr33 adopts a substantially different position in FabXol¹ (gray). (c) In the FabXol3 structure (pink), CDRH3 adopts a different conformation compared with that in the FabXol¹ structure (gray). (d) The conformation adopted by CDRH3 in the unbound FabXol3 structure (pink) is similar to that in the FabXol3–IgE-Fc complex (yellow). The surface of the C∊3 domain from the complex is colored orange (Davies et al., 2017

STRUCTURAL BIOLOGY
COMMUNICATIONS

ISSN: 2053-230X

Volume 76| Part 3| March 2020| Pages 116-129

https://doi.org/10.1107/S2053230X20001466

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