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PDBsum entry 2js0

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protein links
Signaling protein PDB id
2js0
Jmol PyMol
Contents
Protein chain
61 a.a. *
* Residue conservation analysis
PDB id:
2js0
Name: Signaling protein
Title: Solution structure of second sh3 domain of adaptor nck
Structure: Cytoplasmic protein nck1. Chain: a. Fragment: sh3 2. Synonym: nck adaptor protein 1, sh2/sh3 adaptor protein nck-alpha. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: nck1, nck. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
NMR struc: 20 models
Authors: M.J.Hake,K.Choowongkomon,C.R.Carlin,F.D.Sonnichsen
Key ref: M.J.Hake et al. (2008). Specificity determinants of a novel Nck interaction with the juxtamembrane domain of the epidermal growth factor receptor. Biochemistry, 47, 3096-3108. PubMed id: 18269246
Date:
29-Jun-07     Release date:   26-Feb-08    
PROCHECK
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 Headers
 References

Protein chain
Pfam   ArchSchema ?
P16333  (NCK1_HUMAN) -  Cytoplasmic protein NCK1
Seq:
Struc:
377 a.a.
61 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 

 
Biochemistry 47:3096-3108 (2008)
PubMed id: 18269246  
 
 
Specificity determinants of a novel Nck interaction with the juxtamembrane domain of the epidermal growth factor receptor.
M.J.Hake, K.Choowongkomon, O.Kostenko, C.R.Carlin, F.D.Sönnichsen.
 
  ABSTRACT  
 
Nck is a ubiquitously expressed adaptor protein containing Src homology 2 (SH2) and Src homology 3 (SH3) domains. It integrates downstream effector proteins with cell membrane receptors, such as the epidermal growth factor receptor (EGFR). EGFR plays a critical role in cellular proliferation and differentiation. The 45-residue juxtamembrane domain of EGFR (JM), located between the transmembrane and kinase domains, regulates receptor activation and trafficking to the basolateral membrane of polarized epithelia through a proline-rich motif that resembles a consensus SH3 domain binding site. We demonstrate here that the JM region can bind to Nck, showing a notable binding preference for the second SH3 domain. To elucidate the structural determinants for this interaction, we have determined the NMR solution structures of both the first and second Nck SH3 domains (Nck1-1 and Nck1-2). These domains adopt a canonical SH3 beta-barrel-like fold, containing five antiparallel strands separated by three loop regions and one 3 10-helical turn. Chemical shift perturbation studies have identified the residues that form the binding cleft of Nck1-2, which are primarily located in the RT and n-Src loops. JM binds to Nck1-2 with an affinity of approximately 80 microM through a positively charged sequence near the N-terminus, as opposed to the polyproline sequence. The two Nck SH3 domains exhibit both steric and electrostatic differences in their RT-Src and n-Src loops, and a model of the Nck1-2 domain complexed with the JM highlights the factors that define the putative binding mode for this ligand.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
19951361 P.Sánchez-González, K.Jellali, and A.Villalobo (2010).
Calmodulin-mediated regulation of the epidermal growth factor receptor.
  FEBS J, 277, 327-342.  
20519437 S.Ryan, S.Verghese, N.L.Cianciola, C.U.Cotton, and C.R.Carlin (2010).
Autosomal recessive polycystic kidney disease epithelial cell model reveals multiple basolateral epidermal growth factor receptor sorting pathways.
  Mol Biol Cell, 21, 2732-2745.  
19361414 A.Severin, R.E.Joseph, S.Boyken, D.B.Fulton, and A.H.Andreotti (2009).
Proline isomerization preorganizes the Itk SH2 domain for binding to the Itk SH3 domain.
  J Mol Biol, 387, 726-743.  
19187548 M.Lettau, J.Pieper, and O.Janssen (2009).
Nck adapter proteins: functional versatility in T cells.
  Cell Commun Signal, 7, 1.  
19034675 R.Schmucki, S.Yokoyama, and P.Güntert (2009).
Automated assignment of NMR chemical shifts using peak-particle dynamics simulation with the DYNASSIGN algorithm.
  J Biomol NMR, 43, 97.  
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.

 

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