PA regions targeted by neutralizing antibodies. PA monomer (left) is cleaved by cellular furin, releasing domain 1a (amino acids 1–167, colored gray), and allowing the remaining domains to assemble into a heptameric channel (right). Domains remaining in the heptamer are 1b (yellow), 2 (red), 3 (blue), and 4 (green). Indicated in black within domain 4 is the “small loop,” amino acids 680–692, which is involved in binding to the PA receptor. The neutralizing mouse mAb 14B7 reacts with this region, preventing PA binding to the receptor. In the heptamer, the “top” of domain 1a contains a surface on which LF and EF bind to initiate internalization. Neutralizing mouse mAb 1G3 binds to this same surface, competing with EF and LF, and thereby blocking their action. This figure was created with Protein Explorer (35), available at http://www.umass.edu/microbio/chime/explorer, using existing PAmonomer and heptamer structure files contained in an Atlas of Macromolecules available at http://www.umass.edu/microbio/chime/explorer/index2.htm.