PMID- 10212266
OWN - NLM
STAT- MEDLINE
DCOM- 19990603
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 18
DP  - 1999 Apr 30
TI  - Replacement of threonine 558, a critical site of phosphorylation of moesin in
      vivo, with aspartate activates F-actin binding of moesin. Regulation by
      conformational change.
PG  - 12803-10
AB  - Point and deletion mutants of moesin were examined for F-actin binding by blot
      overlay and co-sedimentation, and for intra- and intermolecular interactions with
      N- and C-terminal domains with yeast two-hybrid and in vitro binding assays.
      Wild-type moesin molecules interact poorly with F-actin and each other, and bind 
      neither C- nor N-terminal fragments. Interaction with F-actin is strongly
      enhanced by replacement of Thr558 with aspartate (T558D), by deletion of 11
      N-terminal residues (DelN11), by deletion of the entire N-terminal
      membrane-binding domain of both wild type and T558D mutant molecules, and by
      exposure to phosphatidylinositol 4, 5-diphosphate. Activation of F-actin binding 
      is accompanied by changes in inter- and intramolecular domain interactions. The
      T558D mutation renders moesin capable of binding wild type but not mutated
      (T558D) C-terminal or wild type N-terminal fragments. The interaction between the
      latter two is prevented. DelN11 truncation enables binding of wild type N and C
      domain fragments. These changes suggest that the T558D mutation, mimicking
      phosphorylation of Thr558, promotes F-actin binding by disruption of interdomain 
      interactions between N and C domains and exposure of the high affinity F-actin
      binding site in the C-terminal domain. Oscillation between activated and resting 
      state could thus provide the structural basis for transient interactions between 
      moesin and the actin cytoskeleton in protruding and retracting microextensions.
FAU - Huang, L
AU  - Huang L
AD  - Molecular Mechanisms of Disease Laboratories, Department of Pathology, Stanford
      University School of Medicine, Stanford, California 94305-5324, USA.
FAU - Wong, T Y
AU  - Wong TY
FAU - Lin, R C
AU  - Lin RC
FAU - Furthmayr, H
AU  - Furthmayr 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 (Actins)
RN  - 0 (DNA Primers)
RN  - 0 (Microfilament Proteins)
RN  - 144131-77-1 (moesin)
RN  - 2ZD004190S (Threonine)
RN  - 30KYC7MIAI (Aspartic Acid)
SB  - IM
MH  - Actins/*metabolism
MH  - Amino Acid Substitution
MH  - Aspartic Acid/chemistry/*metabolism
MH  - Base Sequence
MH  - DNA Primers
MH  - Humans
MH  - Microfilament Proteins/chemistry/genetics/*metabolism
MH  - Mutagenesis, Site-Directed
MH  - Phosphorylation
MH  - Protein Binding
MH  - Threonine/chemistry/*metabolism
EDAT- 1999/04/23 00:00
MHDA- 1999/04/23 00:01
CRDT- 1999/04/23 00:00
PHST- 1999/04/23 00:00 [pubmed]
PHST- 1999/04/23 00:01 [medline]
PHST- 1999/04/23 00:00 [entrez]
AID - 10.1074/jbc.274.18.12803 [doi]
AID - S0021-9258(19)73421-8 [pii]
PST - ppublish
SO  - J Biol Chem. 1999 Apr 30;274(18):12803-10. doi: 10.1074/jbc.274.18.12803.