PMID- 10455184
OWN - NLM
STAT- MEDLINE
DCOM- 19990930
LR  - 20190508
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 35
DP  - 1999 Aug 27
TI  - Tetratricopeptide repeat (TPR) motifs of p67(phox) participate in interaction
      with the small GTPase Rac and activation of the phagocyte NADPH oxidase.
PG  - 25051-60
AB  - The small GTPase Rac functions as a molecular switch in several important
      cellular events including cytoskeletal reorganization and activation of the
      phagocyte NADPH oxidase, the latter of which leads to production of superoxide, a
      precursor of microbicidal oxidants. During formation of the active oxidase
      complex at the membrane, the GTP-bound Rac appears to interact with the
      N-terminal region of p67(phox), another indispensable activator that translocates
      from the cytosol upon phagocyte stimulation. Here we show that the p67(phox) N
      terminus lacks the CRIB motif, a well known Rac target, but contains four
      tetratricopeptide repeat (TPR) motifs with highly alpha-helical structure.
      Disruption of any of the N-terminal three TPRs, but the last one, results in
      defective interaction with Rac, while all the four are required for the NADPH
      oxidase activation. We also find that Arg-102 in the third repeat is likely
      involved in binding to Rac via an ionic interaction, and that replacement of this
      residue with Glu completely abrogates the capability of activating the oxidase
      both in vivo and in vitro. Thus the TPR motifs of p67(phox) are packed to
      function as a Rac target, thereby playing a crucial role in the active oxidase
      complex formation.
FAU - Koga, H
AU  - Koga H
AD  - Department of Molecular and Structural Biology, Kyushu University Graduate School
      of Medical Science, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
FAU - Terasawa, H
AU  - Terasawa H
FAU - Nunoi, H
AU  - Nunoi H
FAU - Takeshige, K
AU  - Takeshige K
FAU - Inagaki, F
AU  - Inagaki F
FAU - Sumimoto, H
AU  - Sumimoto H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Phosphoproteins)
RN  - 0 (Recombinant Proteins)
RN  - 0 (neutrophil cytosol factor 67K)
RN  - EC 1.6.3.- (NADPH Oxidases)
RN  - EC 3.6.1.- (GTP-Binding Proteins)
RN  - EC 3.6.5.2 (rac GTP-Binding Proteins)
SB  - IM
MH  - Circular Dichroism
MH  - Enzyme Activation
MH  - GTP-Binding Proteins/genetics/*metabolism
MH  - Humans
MH  - K562 Cells
MH  - Magnetic Resonance Spectroscopy
MH  - Mutagenesis
MH  - NADPH Oxidases/*metabolism
MH  - Neutrophils/*enzymology
MH  - Phagocytes/enzymology
MH  - Phosphoproteins/chemistry/genetics/*metabolism
MH  - Protein Binding
MH  - Protein Structure, Secondary
MH  - Recombinant Proteins/genetics
MH  - *Repetitive Sequences, Nucleic Acid
MH  - Sequence Alignment
MH  - Transfection
MH  - Yeasts/genetics
MH  - rac GTP-Binding Proteins
EDAT- 1999/08/24 00:00
MHDA- 1999/08/24 00:01
CRDT- 1999/08/24 00:00
PHST- 1999/08/24 00:00 [pubmed]
PHST- 1999/08/24 00:01 [medline]
PHST- 1999/08/24 00:00 [entrez]
AID - 10.1074/jbc.274.35.25051 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 Aug 27;274(35):25051-60. doi: 10.1074/jbc.274.35.25051.