PDBsum entry 1neb

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Sh3 domain PDB id
Protein chain
60 a.a. *
* Residue conservation analysis
PDB id:
Name: Sh3 domain
Title: Sh3 domain from human nebulin, nmr, minimized average structure
Structure: Nebulin. Chain: a. Fragment: sh3 domain. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Cell_line: bl21. Expressed in: escherichia coli. Expression_system_taxid: 562.
NMR struc: 1 models
Authors: A.S.Politou,A.Pastore
Key ref:
A.S.Politou et al. (1998). SH3 in muscles: solution structure of the SH3 domain from nebulin. J Mol Biol, 276, 189-202. PubMed id: 9514727 DOI: 10.1006/jmbi.1997.1521
07-Aug-97     Release date:   24-Dec-97    
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Protein chain
Pfam   ArchSchema ?
P20929  (NEBU_HUMAN) -  Nebulin
6669 a.a.
60 a.a.
Key:    PfamA domain  Secondary structure  CATH domain


DOI no: 10.1006/jmbi.1997.1521 J Mol Biol 276:189-202 (1998)
PubMed id: 9514727  
SH3 in muscles: solution structure of the SH3 domain from nebulin.
A.S.Politou, S.Millevoi, M.Gautel, B.Kolmerer, A.Pastore.
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.
  Selected figure(s)  
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.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
  19789381 A.Kontrogianni-Konstantopoulos, M.A.Ackermann, A.L.Bowman, S.V.Yap, and R.J.Bloch (2009).
Muscle giants: molecular scaffolds in sarcomerogenesis.
  Physiol Rev, 89, 1217-1267.  
19633357 P.Fernando, J.S.Sandoz, W.Ding, Repentigny, S.Brunette, J.F.Kelly, R.Kothary, and L.A.Megeney (2009).
Bin1 SRC homology 3 domain acts as a scaffold for myofiber sarcomere assembly.
  J Biol Chem, 284, 27674-27686.  
16902413 C.C.Witt, C.Burkart, D.Labeit, M.McNabb, Y.Wu, H.Granzier, and S.Labeit (2006).
Nebulin regulates thin filament length, contractility, and Z-disk structure in vivo.
  EMBO J, 25, 3843-3855.  
16766517 K.Ma, J.G.Forbes, G.Gutierrez-Cruz, and K.Wang (2006).
Titin as a giant scaffold for integrating stress and Src homology domain 3-mediated signaling pathways: the clustering of novel overlap ligand motifs in the elastic PEVK segment.
  J Biol Chem, 281, 27539-27556.  
15004028 B.Li, L.Zhuang, and B.Trueb (2004).
Zyxin interacts with the SH3 domains of the cytoskeletal proteins LIM-nebulette and Lasp-1.
  J Biol Chem, 279, 20401-20410.  
11170442 D.D.Root, and K.Wang (2001).
High-affinity actin-binding nebulin fragments influence the actoS1 complex.
  Biochemistry, 40, 1171-1186.  
11316885 K.V.Kishan, M.E.Newcomer, T.H.Rhodes, and S.D.Guilliot (2001).
Effect of pH and salt bridges on structural assembly: molecular structures of the monomer and intertwined dimer of the Eps8 SH3 domain.
  Protein Sci, 10, 1046-1055.
PDB codes: 1i07 1i0c
  11206067 A.Rath, and A.R.Davidson (2000).
The design of a hyperstable mutant of the Abp1p SH3 domain by sequence alignment analysis.
  Protein Sci, 9, 2457-2469.  
10931867 K.Ojima, Z.X.Lin, M.Bang, S.Holtzer, R.Matsuda, S.Labeit, H.L.Sweeney, and H.Holtzer (2000).
Distinct families of Z-line targeting modules in the COOH-terminal region of nebulin.
  J Cell Biol, 150, 553-566.  
10574999 W.L.Lee, E.M.Ostap, H.G.Zot, and T.D.Pollard (1999).
Organization and ligand binding properties of the tail of Acanthamoeba myosin-IA. Identification of an actin-binding site in the basic (tail homology-1) domain.
  J Biol Chem, 274, 35159-35171.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.