Structure and activity of the axon guidance protein MICAL

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

doi:10.1073/pnas.0504838102

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 journal › Article › peer-review

72 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 MICAL_fd is an FAD-containing module structurally similar to aromatic hydroxylases and amine oxidases. In addition, we present biochemical data that show that MICAL_fd is a flavoenzyme that in the presence of NADPH reduces molecular oxygen to H₂O₂ (K _m,NAPDH = 222 μM; k_cat = 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 language	English (US)
Pages (from-to)	16830-16835
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	102
Issue number	46
DOIs	https://doi.org/10.1073/pnas.0504838102
State	Published - Nov 15 2005
Externally published	Yes

Keywords

Hydrogen peroxide
Hydroxylase
Monooxygenase
X-ray diffraction

ASJC Scopus subject areas

General

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10.1073/pnas.0504838102

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title = "Structure and activity of the axon guidance protein MICAL",

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 {\AA} 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.",

keywords = "Hydrogen peroxide, Hydroxylase, Monooxygenase, X-ray diffraction",

author = "Mythili Nadella and Bianchet, \{Mario A.\} and Gabelli, \{Sandra B.\} and Jennifer Barrila and Amzel, \{L. Mario\}",

year = "2005",

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doi = "10.1073/pnas.0504838102",

language = "English (US)",

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journal = "Proceedings of the National Academy of Sciences of the United States of America",

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publisher = "National Academy of Sciences",

number = "46",

}

TY - JOUR

T1 - Structure and activity of the axon guidance protein MICAL

AU - Nadella, Mythili

AU - Bianchet, Mario A.

AU - Gabelli, Sandra B.

AU - Barrila, Jennifer

AU - Amzel, L. Mario

PY - 2005/11/15

Y1 - 2005/11/15

N2 - 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.

AB - 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.

KW - Hydrogen peroxide

KW - Hydroxylase

KW - Monooxygenase

KW - X-ray diffraction

UR - https://www.scopus.com/pages/publications/28044451974

UR - https://www.scopus.com/pages/publications/28044451974#tab=citedBy

U2 - 10.1073/pnas.0504838102

DO - 10.1073/pnas.0504838102

M3 - Article

C2 - 16275926

AN - SCOPUS:28044451974

SN - 0027-8424

VL - 102

SP - 16830

EP - 16835

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

IS - 46

ER -

Structure and activity of the axon guidance protein MICAL

Abstract

Keywords

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