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J. Biol. Chem., Vol. 278, Issue 7, 4949-4956, February 14, 2003
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From the Ezrin is a member of the ERM (ezrin,
radixin, moesin) family of proteins that
cross-link the actin cytoskeleton to the plasma membrane and also may
function in signaling cascades that regulate the assembly of actin
stress fibers. Here, we report a crystal structure for the free
(activated) FERM domain (residues 2-297) of recombinant human ezrin at
2.3 Å resolution. Structural comparison among the dormant moesin FERM
domain structure and the three known active FERM domain structures
(radixin, moesin, and now ezrin) allows the clear definition of regions
that undergo structural changes during activation. The key regions
affected are residues 135-150 and 155-180 in lobe F2 and residues
210-214 and 235-267 in lobe F3. Furthermore, we show that a large
increase in the mobilities of lobes F2 and F3 accompanies activation,
suggesting that their integrity is compromised. This leads us to
propose a new concept that we refer to as keystone interactions.
Keystone interactions occur when one protein (or protein part)
contributes residues that allow another protein to complete folding,
meaning that it becomes an integral part of the structure and would
rarely dissociate. Such interactions are well suited for long-lived
cytoskeletal protein interactions. The keystone interactions
concept leads us to predict two specific docking sites within lobes F2
and F3 that are likely to bind target proteins.
The atomic coordinates and the structure factors (code 1NI2) have been deposited in the Protein Data Bank, Research Collaboratory for Structural Bioinformatics, Rutgers University, New Brunswick, NJ (http://www.rcsb.org/).
Structure of the Active N-terminal Domain of Ezrin
CONFORMATIONAL AND MOBILITY CHANGES IDENTIFY KEYSTONE
INTERACTIONS*
,§,
,**, and§§
Departments of Chemistry and Chemical
Biology, ¶ Molecular Biology and Genetics, and
** Molecular Medicine, Cornell University, Ithaca, New York
14853 and the Department of Biochemistry and
Biophysics, Oregon State University, Corvallis, Oregon 97331
*
This work is based upon research conducted at the Cornell
High Energy Synchrotron Source (CHESS), which is supported by the National Science Foundation and NIGMS, National Institutes of Health
under award DMR 9713424. This work was supported by National Institutes
of Health Grants GM36652 (to A. P. B.) and 2 R01 GM40654 (to
R. A. C.) and NIH Training Grant GM07273 (to W. J. S.).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence may be addressed. Tel.: 607-255-5713;
Fax: 607-255-6249; E-mail: apb5@cornell.edu.
§§
To whom correspondence may be addressed. Tel.: 541-737-3200; Fax:
541-737-0481; E-mail: karplusp@ucs.orst.edu.
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