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PDBsum entry 1u5s

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protein metals Protein-protein interface(s) links
Metal binding protein PDB id
1u5s
Jmol
Contents
Protein chains
71 a.a. *
66 a.a. *
Metals
_ZN ×2
* Residue conservation analysis
PDB id:
1u5s
Name: Metal binding protein
Title: Nmr structure of the complex between nck-2 sh3 domain and pinch-1 lim4 domain
Structure: Cytoplasmic protein nck2. Chain: a. Fragment: third sh3 domain (residues 192-262). Synonym: nck adaptor protein 2, sh2/sh3 adaptor protein nck-beta, nck-2. Engineered: yes. Pinch protein. Chain: b. Fragment: fourth lim domain (residues 188-251).
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: nck2. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Gene: lims1.
NMR struc: 18 models
Authors: J.Vaynberg,T.Fukuda,O.Vinogradova,A.Velyvis,L.Ng,C.Wu,J.Qin
Key ref:
J.Vaynberg et al. (2005). Structure of an ultraweak protein-protein complex and its crucial role in regulation of cell morphology and motility. Mol Cell, 17, 513-523. PubMed id: 15721255 DOI: 10.1016/j.molcel.2004.12.031
Date:
28-Jul-04     Release date:   05-Apr-05    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
O43639  (NCK2_HUMAN) -  Cytoplasmic protein NCK2
Seq:
Struc:
380 a.a.
71 a.a.
Protein chain
Pfam   ArchSchema ?
P48059  (LIMS1_HUMAN) -  LIM and senescent cell antigen-like-containing domain protein 1
Seq:
Struc:
325 a.a.
66 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Biochemical function     zinc ion binding     1 term  

 

 
DOI no: 10.1016/j.molcel.2004.12.031 Mol Cell 17:513-523 (2005)
PubMed id: 15721255  
 
 
Structure of an ultraweak protein-protein complex and its crucial role in regulation of cell morphology and motility.
J.Vaynberg, T.Fukuda, K.Chen, O.Vinogradova, A.Velyvis, Y.Tu, L.Ng, C.Wu, J.Qin.
 
  ABSTRACT  
 
Weak protein-protein interactions (PPIs) (K(D) > 10(-6) M) are critical determinants of many biological processes. However, in contrast to a large growing number of well-characterized, strong PPIs, the weak PPIs, especially those with K(D) > 10(-4) M, are poorly explored. Genome wide, there exist few 3D structures of weak PPIs with K(D) > 10(-4) M, and none with K(D) > 10(-3) M. Here, we report the NMR structure of an extremely weak focal adhesion complex (K(D) approximately 3 x 10(-3) M) between Nck-2 SH3 domain and PINCH-1 LIM4 domain. The structure exhibits a remarkably small and polar interface with distinct binding modes for both SH3 and LIM domains. Such an interface suggests a transient Nck-2/PINCH-1 association process that may trigger rapid focal adhesion turnover during integrin signaling. Genetic rescue experiments demonstrate that this interface is indeed involved in mediating cell shape change and migration. Together, the data provide a molecular basis for an ultraweak PPI in regulating focal adhesion dynamics during integrin signaling.
 
  Selected figure(s)  
 
Figure 2.
Figure 2. Distinct Binding Modes of SH3-3 and LIM4 Domains(A) Sequence alignment for SH3-3 and LIM4 with other representative homologs. For representative SH3 domains, CSK (Ghose et al., 2001), p67^phox (Kami et al., 2002), and ScPex13P (Pires et al., 2003) were chosen based on the fact that their crystal structures are available for comparison and that the former two recognize conventional PXXP motifs and the last recognizes a nonconventional sequence. Note that the recognition sequences for Csk and p67phox are not in Table 2 (only non-PxxP binding sequences are in Table 2). Also, although residues marked in blue are essential for PXXP binding, other neighboring residues in the sequence could be potentially involved in binding to immediate regions of the N or C terminus of the PXXP ligand. For the LIM domain, PINCH LIM1 and LMO4 were chosen because their binding modes have been published (Velyvis et al. 2001; Velyvis et al. 2003 and Deane et al. 2003). The binding interface residues for Nck-2 SH3-3 are marked in red and are contrasted to conventional PxxP binding sites in CSK_Hum and p67^phox_Hum (blue), nonconventional binding sites in CSK_Hum and p67^phox_Hum (orange), and ScPex13P (magenta). The binding interface residues for PINCH-1 LIM4 are marked in red and are contrasted to those in PINCH-1 LIM1 and LMO4 (green).(B) The conventional and nonconventional binding site residues for SH3 domains in (A) are projected to the SH3-3 surface. PPII: conventional PxxP ligand binding site. Both CSK and p67phox SH3 domains have conventional and nonconventional binding sites. ScPex13P SH3 has an entirely nonconventional binding mode (magenta), which is better seen by rotating the surface 90° counterclockwise around the z axis. However, all of these binding sites are different from the Nck-2 SH3-3 binding site by LIM4.(C) The binding site residues for the LIM domains in (A) are projected to the PINCH-1 LIM4 surface, showing that the LIM4 binding site for SH3-3 is distinct from those of LMO4 and PINCH-1 LIM1.
Figure 6.
Figure 6. Diagram of a Complex Network Involved in the Cell-Matrix Adhesion Regulation of Actin CytoskeletonThe complex network that involves PINCH-1 and Nck-2 provides insight into how the ultraweak Nck-2/PINCH-1 interaction transiently contributes to the stability and dynamics of the supermolecular complex. The transient association of Nck-2/PINCH-1 may facilitate the rapid assembly/disassembly of the complex during cell shape modulation and movement. All proteins labeled in the diagram have been shown to be involved in the network (see reviews by Wu 1999; Wu and Dedhar 2001; Buday et al. 2002 and Brakebusch and Fassler 2003). The list of proteins in the network is expected to continue to grow.
 
  The above figures are reprinted by permission from Cell Press: Mol Cell (2005, 17, 513-523) copyright 2005.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21338686 A.J.Rowe (2011).
Ultra-weak reversible protein-protein interactions.
  Methods, 54, 157-166.  
20945343 J.Kovalevich, B.Tracy, and D.Langford (2011).
PINCH: More than just an adaptor protein in cellular response.
  J Cell Physiol, 226, 940-947.  
21214861 M.Bieri, A.H.Kwan, M.Mobli, G.F.King, J.P.Mackay, and P.R.Gooley (2011).
Macromolecular NMR spectroscopy for the non-spectroscopist: beyond macromolecular solution structure determination.
  FEBS J, 278, 704-715.  
21131971 P.Sarkar, T.Saleh, S.R.Tzeng, R.B.Birge, and C.G.Kalodimos (2011).
Structural basis for regulation of the Crk signaling protein by a proline switch.
  Nat Chem Biol, 7, 51-57.
PDB codes: 2l3p 2l3q 2l3s
20530873 I.Eke, U.Koch, S.Hehlgans, V.Sandfort, F.Stanchi, D.Zips, M.Baumann, A.Shevchenko, C.Pilarsky, M.Haase, G.B.Baretton, V.Calleja, B.Larijani, R.Fässler, and N.Cordes (2010).
PINCH1 regulates Akt1 activation and enhances radioresistance by inhibiting PP1alpha.
  J Clin Invest, 120, 2516-2527.  
20334923 S.P.Persaud, D.L.Donermeyer, K.S.Weber, D.M.Kranz, and P.M.Allen (2010).
High-affinity T cell receptor differentiates cognate peptide-MHC and altered peptide ligands with distinct kinetics and thermodynamics.
  Mol Immunol, 47, 1793-1801.  
20368734 Z.Charlop-Powers, L.Zeng, Q.Zhang, and M.M.Zhou (2010).
Structural insights into selective histone H3 recognition by the human Polybromo bromodomain 2.
  Cell Res, 20, 529-538.
PDB codes: 2ktb 3ljw
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.  
19895269 I.Eke, S.Hehlgans, and N.Cordes (2009).
There's something about ILK.
  Int J Radiat Biol, 85, 929-936.  
19117955 Y.Yang, X.Wang, C.A.Hawkins, K.Chen, J.Vaynberg, X.Mao, Y.Tu, X.Zuo, J.Wang, Y.X.Wang, C.Wu, N.Tjandra, and J.Qin (2009).
Structural Basis of Focal Adhesion Localization of LIM-only Adaptor PINCH by Integrin-linked Kinase.
  J Biol Chem, 284, 5836-5844.  
19074270 B.P.Chiswell, R.Zhang, J.W.Murphy, T.J.Boggon, and D.A.Calderwood (2008).
The structural basis of integrin-linked kinase-PINCH interactions.
  Proc Natl Acad Sci U S A, 105, 20677-20682.
PDB code: 3f6q
18555270 K.Takeuchi, H.Yang, E.Ng, S.Y.Park, Z.Y.Sun, E.L.Reinherz, and G.Wagner (2008).
Structural and functional evidence that Nck interaction with CD3epsilon regulates T-cell receptor activity.
  J Mol Biol, 380, 704-716.
PDB code: 2jxb
18054235 P.Tompa, and M.Fuxreiter (2008).
Fuzzy complexes: polymorphism and structural disorder in protein-protein interactions.
  Trends Biochem Sci, 33, 2-8.  
18508764 X.Wang, K.Fukuda, I.J.Byeon, A.Velyvis, C.Wu, A.Gronenborn, and J.Qin (2008).
The structure of alpha-parvin CH2-paxillin LD1 complex reveals a novel modular recognition for focal adhesion assembly.
  J Biol Chem, 283, 21113-21119.
PDB code: 2k2r
17192269 A.Ababou, M.Gautel, and M.Pfuhl (2007).
Dissecting the N-terminal myosin binding site of human cardiac myosin-binding protein C. Structure and myosin binding of domain C2.
  J Biol Chem, 282, 9204-9215.
PDB code: 1pd6
17434495 A.Pierres, A.Prakasam, D.Touchard, A.M.Benoliel, P.Bongrand, and D.Leckband (2007).
Dissecting subsecond cadherin bound states reveals an efficient way for cells to achieve ultrafast probing of their environment.
  FEBS Lett, 581, 1841-1846.  
17699158 B.Sot, S.M.Freund, and A.R.Fersht (2007).
Comparative biophysical characterization of p53 with the pro-apoptotic BAK and the anti-apoptotic BCL-xL.
  J Biol Chem, 282, 29193-29200.  
17289588 P.Sarkar, C.Reichman, T.Saleh, R.B.Birge, and C.G.Kalodimos (2007).
Proline cis-trans isomerization controls autoinhibition of a signaling protein.
  Mol Cell, 25, 413-426.  
17591694 S.Guan, M.Chen, D.Woodley, and W.Li (2007).
Nckbeta adapter controls neuritogenesis by maintaining the cellular paxillin level.
  Mol Cell Biol, 27, 6001-6011.  
17084981 S.Hehlgans, M.Haase, and N.Cordes (2007).
Signalling via integrins: implications for cell survival and anticancer strategies.
  Biochim Biophys Acta, 1775, 163-180.  
17074767 H.Chen, D.M.Choudhury, and S.W.Craig (2006).
Coincidence of actin filaments and talin is required to activate vinculin.
  J Biol Chem, 281, 40389-40398.  
16314921 J.L.Sepulveda, and C.Wu (2006).
The parvins.
  Cell Mol Life Sci, 63, 25-35.  
16216358 J.Vaynberg, and J.Qin (2006).
Weak protein-protein interactions as probed by NMR spectroscopy.
  Trends Biotechnol, 24, 22-27.  
16493410 K.R.Legate, E.Montañez, O.Kudlacek, and R.Fässler (2006).
ILK, PINCH and parvin: the tIPP of integrin signalling.
  Nat Rev Mol Cell Biol, 7, 20-31.  
16644733 M.R.Schiller, K.Chakrabarti, G.F.King, N.I.Schiller, B.A.Eipper, and M.W.Maciejewski (2006).
Regulation of RhoGEF activity by intramolecular and intermolecular SH3 domain interactions.
  J Biol Chem, 281, 18774-18786.
PDB code: 1u3o
16699013 N.L.Teterina, E.Levenson, M.S.Rinaudo, D.Egger, K.Bienz, A.E.Gorbalenya, and E.Ehrenfeld (2006).
Evidence for functional protein interactions required for poliovirus RNA replication.
  J Virol, 80, 5327-5337.  
16604428 S.Park, K.Takeuchi, and G.Wagner (2006).
Solution structure of the first SRC homology 3 domain of human Nck2.
  J Biomol NMR, 34, 203-208.
PDB code: 2b86
16505963 Y.Xu, X.Wang, J.Yang, J.Vaynberg, and J.Qin (2006).
PASA--a program for automated protein NMR backbone signal assignment by pattern-filtering approach.
  J Biomol NMR, 34, 41-56.  
16122968 A.M.Bonvin, R.Boelens, and R.Kaptein (2005).
NMR analysis of protein interactions.
  Curr Opin Chem Biol, 9, 501-508.  
16301539 M.H.Suh, P.Ye, M.Zhang, S.Hausmann, S.Shuman, A.L.Gnatt, and J.Fu (2005).
Fcp1 directly recognizes the C-terminal domain (CTD) and interacts with a site on RNA polymerase II distinct from the CTD.
  Proc Natl Acad Sci U S A, 102, 17314-17319.  
15941716 Z.Xu, T.Fukuda, Y.Li, X.Zha, J.Qin, and C.Wu (2005).
Molecular dissection of PINCH-1 reveals a mechanism of coupling and uncoupling of cell shape modulation and survival.
  J Biol Chem, 280, 27631-27637.  
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.