PDBsum entry 2frw

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protein links
Protein binding PDB id
Jmol PyMol
Protein chain
57 a.a. *
* Residue conservation analysis
PDB id:
Name: Protein binding
Title: Solution structure of the second sh3 domain of human adaptor protein nck2
Structure: Cytoplasmic protein nck2. Chain: a. Fragment: sh3_2. Synonym: nck adaptor protein 2, sh2/sh3 adaptor protein nck-beta, nck-2. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693.
NMR struc: 10 models
Authors: J.Liu
Key ref:
J.Liu et al. (2006). Structural insight into the binding diversity between the human Nck2 SH3 domains and proline-rich proteins. Biochemistry, 45, 7171-7184. PubMed id: 16752908 DOI: 10.1021/bi060091y
20-Jan-06     Release date:   20-Jun-06    
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Protein chain
Pfam   ArchSchema ?
O43639  (NCK2_HUMAN) -  Cytoplasmic protein NCK2
380 a.a.
57 a.a.
Key:    PfamA domain  Secondary structure  CATH domain


DOI no: 10.1021/bi060091y Biochemistry 45:7171-7184 (2006)
PubMed id: 16752908  
Structural insight into the binding diversity between the human Nck2 SH3 domains and proline-rich proteins.
J.Liu, M.Li, X.Ran, J.S.Fan, J.Song.
Human Nck2 (hNck2) is a 380-residue adapter protein consisting of three SH3 domains and one SH2 domain. Nck2 plays a pivotal role in connecting and integrating signaling networks constituted by transmembrane receptors such as ephrinB and effectors critical for cytoskeletonal dynamics and remodeling. In this study, we aimed to determine the NMR structures and dynamic properties of the hNck2 SH3 domains and to define their ligand binding preferences with nine proline-rich peptides derived from Wire, CAP-1, CAP-2, Prk, Wrch1, Wrch2, and Nogo. The results indicate (1) the first hNck2 SH3 domain is totally insoluble. On the other hand, although the second and third hNck2 SH3 domains adopt a conserved SH3 fold, they exhibit distinctive dynamic properties. Interestingly, the third SH3 domain has a far-UV CD spectrum typical of a largely unstructured protein but exhibits {1H}-15N steady-state NOE values larger than 0.7 for most residues. (2) The HSQC titrations revealed that the two SH3 domains have differential ligand preferences. The second SH3 domain seems to prefer a consensus sequence of APx#PxR, while the third SH3 domain prefers PxAPxR. (3) Several high-affinity bindings were identified for hNck2 SH3 domains by isothermal titration calorimetry. In particular, the binding of SH3-3 with the Nogo-A peptide was discovered and shown to exhibit a Kd of 5.7 microM. Interestingly, of the three SH3-binding motifs carried by Wrch1, only the middle one was capable of binding SH3-2. Our results provide valuable clues for further functional investigations into the Nck2-mediated signaling networks.

Literature references that cite this PDB file's key reference

  PubMed id Reference
19956763 J.Liu, and J.Song (2009).
Insights into protein aggregation by NMR characterization of insoluble SH3 mutants solubilized in salt-free water.
  PLoS One, 4, e7805.  
19187548 M.Lettau, J.Pieper, and O.Janssen (2009).
Nck adapter proteins: functional versatility in T cells.
  Cell Commun Signal, 7, 1.  
18708347 H.Qin, J.Shi, R.Noberini, E.B.Pasquale, and J.Song (2008).
Crystal structure and NMR binding reveal that two small molecule antagonists target the high affinity ephrin-binding channel of the EphA4 receptor.
  J Biol Chem, 283, 29473-29484.
PDB code: 3ckh
18599634 J.Liu, and J.Song (2008).
NMR evidence for forming highly populated helical conformations in the partially folded hNck2 SH3 domain.
  Biophys J, 95, 4803-4812.  
18394700 J.Shi, S.Lua, N.Du, X.Liu, and J.Song (2008).
Identification, recombinant production and structural characterization of four silk proteins from the Asiatic honeybee Apis cerana.
  Biomaterials, 29, 2820-2828.  
18200608 O.Okhrimenko, and I.Jelesarov (2008).
A survey of the year 2006 literature on applications of isothermal titration calorimetry.
  J Mol Recognit, 21, 1.  
18300229 X.Ran, H.Qin, J.Liu, J.S.Fan, J.Shi, and J.Song (2008).
NMR structure and dynamics of human ephrin-B2 ectodomain: the functionally critical C-D and G-H loops are highly dynamic in solution.
  Proteins, 72, 1019-1029.  
17397058 M.Li, and J.Song (2007).
The N- and C-termini of the human Nogo molecules are intrinsically unstructured: bioinformatics, CD, NMR characterization, and functional implications.
  Proteins, 68, 100-108.  
16980357 M.Li, J.Liu, X.Ran, M.Fang, J.Shi, H.Qin, J.M.Goh, and J.Song (2006).
Resurrecting abandoned proteins with pure water: CD and NMR studies of protein fragments solubilized in salt-free water.
  Biophys J, 91, 4201-4209.  
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