 |
PDBsum entry 1neb
|
|
|
|
References listed in PDB file
|
 |
|
Key reference
|
|
|
Title
|
|
Sh3 in muscles: solution structure of the sh3 domain from nebulin.
|
|
|
Authors
|
|
A.S.Politou,
S.Millevoi,
M.Gautel,
B.Kolmerer,
A.Pastore.
|
|
|
Ref.
|
|
J Mol Biol, 1998,
276,
189-202.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
Note In the PDB file this reference is
annotated as "TO BE PUBLISHED".
The citation details given above were identified by an automated
search of PubMed on title and author
names, giving a
perfect match.
|
|
|
|
Abstract
|
|
|
The huge modular protein nebulin is located in the thin filament of striated
muscle in vertebrates and is thought to bind and stabilize F-actin. The
C-terminal part of human nebulin is anchored in the sarcomeric Z-disk and
contains an SH3 domain, the first of such motifs to be identified in a
myofibrillar protein. We have determined the nebulin SH3 sequence from several
species and found it strikingly conserved. We have also shown that the SH3
transcripts are constitutively expressed in skeletal muscle tissues. As the
first step towards a molecular understanding of nebulin's cellular role we have
determined the three-dimensional structure of the human nebulin SH3 domain in
solution by nuclear magnetic resonance (NMR) spectroscopy and compared it with
other known SH3 structures. The nebulin SH3 domain has a well-defined structure
in solution with a typical SH3 topology, consisting of a beta-sandwich of two
triple-stranded, antiparallel beta-sheets arranged at right angles to each other
and of a single turn of a 310-helix. An additional double-stranded antiparallel
beta-sheet in the RT loop bends over the beta-sandwich. The derived structure
reveals a remarkable similarity with a distinct subset of SH3 domains,
especially in the structural features of the exposed hydrophobic patch that is
thought to be the site of interaction with polyproline ligands. On the basis of
this similarity, we have modelled the interaction with an appropriate
polyproline ligand and attempted to delineate the characteristics of the
physiological SH3-binding partner in the Z-disk. Our results represent the first
step in reconstructing the structure of nebulin and are expected to contribute
to our understanding of nebulin's functional role in myofibrillar assembly.
|
|
|
|
|
|
|
|
Figure 5.
Figure 5. Solution structure of nebulin SH3. (a) Stereoview
of the best 15 structures superimposed on backbone atoms (N,
C^α, C′, O) of the β-sheet regions. (b) MOLSCRIPT
representation of the minimized average structure. The
β-strands are colored according to the sheet to which they
belong, βI (cyan), βII (magenta) and βIII (green). The
orientations of the SH3 domain in (a) and (b) are the same.
|
|
Figure 7.
Figure 7. A model of the complexed nebulin SH3. In magenta
the average nebulin SH3 structure, in orange the peptide-ligand.
The residues of the hydrophobic patch are shown in cyan and the
acidic side-chains potentially interacting with the basic groups
of the ligand peptide in green. The ligand peptide is oriented
from bottom (N terminus) to top.
|
|
|
|
|
|
The above figures are
reprinted
by permission from Elsevier:
J Mol Biol
(1998,
276,
189-202)
copyright 1998.
|
|
|
|
|
|
|
