Structure and Activity of the Axon Guidance Protein MICAL
During development, neurons are guided to their targets by short- and long-range attractive and repulsive cues. MICAL, a large multidomain protein, is required for the combined action of semaphorins and plexins in axon guidance. Here, we present the structure of the N-terminal region of MICAL (MICAL{sub fd}) determined by x-ray diffraction to 2.0 Angstrom resolution. The structure shows that MICAL{sub fd} is an FAD-containing module structurally similar to aromatic hydroxylases and amine oxidases. In addition, we present biochemical data that show that MICALfd is a flavoenzyme that in the presence of NADPH reduces molecular oxygen to H{sub 2}O{sub 2} (Km, NAPDH = 222 {micro}M; k{sub cat} = 77 sec{sup -1}), a molecule with known signaling properties. We propose that the H{sub 2}O{sub 2} produced by this reaction may be one of the signaling molecules involved in axon guidance by MICAL.
- Research Organization:
- Brookhaven National Lab. (BNL), Upton, NY (United States). National Synchrotron Light Source
- Sponsoring Organization:
- Doe - Office Of Science
- DOE Contract Number:
- DE-AC02-98CH10886
- OSTI ID:
- 913715
- Report Number(s):
- BNL-78283-2007-JA; PNASA6; TRN: US200804%%169
- Journal Information:
- Proc Natl Acad Sci USA, Vol. 102, Issue 46; ISSN 0027-8424
- Country of Publication:
- United States
- Language:
- English
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