Structure and activity of the axon guidance protein MICAL

Mythili Nadella, Mario A. Bianchet, Sandra B. Gabelli, Jennifer Barrila, L. Mario Amzel

Research output: Contribution to journalArticle

55 Scopus citations

Abstract

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 fd) determined by x-ray diffraction to 2.0 Å resolution. The structure shows that MICALfd 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 H2O2 (K m,NAPDH = 222 μM; kcat = 77 sec-1), a molecule with known signaling properties. We propose that the H 2O2 produced by this reaction may be one of the signaling molecules involved in axon guidance by MICAL.

Original languageEnglish (US)
Pages (from-to)16830-16835
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number46
DOIs
StatePublished - Nov 15 2005
Externally publishedYes

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Keywords

  • Hydrogen peroxide
  • Hydroxylase
  • Monooxygenase
  • X-ray diffraction

ASJC Scopus subject areas

  • General

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