Editors' ChoiceMicrobiology

Anthrax Edema Factor Exploits Calmodulin

See allHide authors and affiliations

Science's STKE  29 Jan 2002:
Vol. 2002, Issue 117, pp. tw43
DOI: 10.1126/stke.2002.117.tw43

Drum et al. have deduced the crystal structure of the anthrax edema factor (EF), a protein containing adenylyl cyclase activity, in the presence or absence of the calcium-binding protein calmodulin (CaM). Apparently, none of the amino acid residues involved with its enzymatic activity are shifted upon association with CaM. Rather, the CaM-dependent conformation shifting that occurs in EF opens the substrate-binding site. A News & Views article by Liddington is most helpful in discussing the biological implications of the mechanism of EF activation. Briefly, when EF associates with CaM, the conformation of CaM is changed sufficiently so that it can no longer bind to its normal intracellular protein partners, thus preventing the CaM-dependent activation of proteins. For example, the ability of Bacillus anthracis-infected macrophages to decrease their intracellular concentration of adenosine-3′,5′-monophosphate (cAMP) is impaired because CaM-dependent phosphodiesterases remain inactive. Increased amounts of cAMP block the function of the transcription factor nuclear factor-κB (NF-κB), a protein involved in signal transduction during immune responses. Additionally, the binding of CaM to EF is required to activate EF's adenylyl cyclase activity, which keeps intracellular (cAMP) concentrations high.

C. L. Drum, S.-Z. Yan, J. Bard, Y.-Q. Shen, D. Lu, S. Soelaiman, Z. Grabarek, A. Bohm, W.-J. Tang, Structural basis for the activation of anthrax adenylyl cyclase exotoxin by calmodulin. Nature 415, 396-402 (2002). [Online Journal]

R. C. Liddington, A molecular full nelson. Nature 415, 373-374 (2002). [Online Journal]

Stay Connected to Science Signaling