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PDBsum entry 2aeh
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protein Protein-protein interface(s) links
Transferase PDB id
2aeh

 

 

 

 

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JSmol PyMol  
Contents
Protein chains
331 a.a. *
Waters ×243
* Residue conservation analysis
PDB id:
2aeh
Name: Transferase
Title: Focal adhesion kinase 1
Structure: Focal adhesion kinase 1. Chain: a, b. Fragment: ferm domain. Synonym: fadk 1, pp125fak. Engineered: yes
Source: Gallus gallus. Chicken. Organism_taxid: 9031. Gene: fak1, fak. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
Resolution:
2.53Å     R-factor:   0.206     R-free:   0.249
Authors: D.F.Ceccarelli,H.K.Song,F.Poy,M.D.Schaller,M.J.Eck
Key ref:
D.F.Ceccarelli et al. (2006). Crystal structure of the FERM domain of focal adhesion kinase. J Biol Chem, 281, 252-259. PubMed id: 16221668 DOI: 10.1074/jbc.M509188200
Date:
22-Jul-05     Release date:   18-Oct-05    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
Q00944  (FAK1_CHICK) -  Focal adhesion kinase 1 from Gallus gallus
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		1053 a.a.
331 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.2.7.10.2  - non-specific protein-tyrosine kinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H+
L-tyrosyl-[protein]
 + ATP
 = O-phospho-L-tyrosyl-[protein]
 + ADP
 + H(+)
Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 

 
    Added reference    
 
 
DOI no: 10.1074/jbc.M509188200 J Biol Chem 281:252-259 (2006)
PubMed id: 16221668  
 
 
Crystal structure of the FERM domain of focal adhesion kinase.
D.F.Ceccarelli, H.K.Song, F.Poy, M.D.Schaller, M.J.Eck.
 
  ABSTRACT  
 
Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that localizes to focal adhesions in adherent cells. Through phosphorylation of proteins assembled at the cytoplasmic tails of integrins, FAK promotes signaling events that modulate cellular growth, survival, and migration. The amino-terminal region of FAK contains a region of sequence homology with band 4.1 and ezrin/radixin/moesin (ERM) proteins termed a FERM domain. FERM domains are found in a variety of signaling and cytoskeletal proteins and are thought to mediate intermolecular interactions with partner proteins and phospholipids at the plasma membrane and intramolecular regulatory interactions. Here we report two crystal structures of an NH2-terminal fragment of avian FAK containing the FERM domain and a portion of the regulatory linker that connects the FERM and kinase domains. The tertiary folds of the three subdomains (F1, F2, and F3) are similar to those of known FERM structures despite low sequence conservation. Differences in the sequence and relative orientation of the F3 subdomain alters the nature of the interdomain interface, and the phosphoinositide binding site found in ERM family FERM domains is not present in FAK. A putative protein interaction site on the F3 lobe is masked by the proximal region of the linker. Additionally, in one structure the adjacent Src SH3 and SH2 binding sites in the linker associate with the surfaces of the F3 and F1 lobes, respectively. These structural features suggest the possibility that protein interactions of the FAK FERM domain can be regulated by binding of Src kinases to the linker segment.
 
  Selected figure(s)  
 
Figure 4.
FIGURE 4. Detailed view of the F3 lobe highlighting the linker interaction. A, ribbon diagram of the FAK F3 lobe with the proximal portion of the linker shown in stick form and colored magenta. The details of this interaction are shown schematically in panel C. B, the radixin F3 lobe (yellow) bound to a peptide representing the cytoplasmic tail of ICAM-2 (gray). C, schematic detailing the interactions of the linker with the putative ligand binding groove on the F3 lobe. Linker residues are indicated in magenta, FERM domain residues in cyan. Dashed lines indicate hydrogen bond interactions and semicircles indicate hydrophobic interactions. Note that the linker also contacts the F1 lobe as indicated. 		Figure 5.
FIGURE 5. Portions of the FERM kinase linker including the Src SH3 binding site and the Tyr397 autophosphorylation site are tethered across the surface of the F1 and F3 subdomains in the FAK405 structure. A, ribbon and transparent surface representation of the FAK FERM domain. The Src SH3 binding site is shown in green (residues 363-375) and the Tyr397-containing segment (residues 394-403) is colored in pink. B, detail of the interactions between the Src SH3-binding site and the surface of F3. Hydrogen bonds between the RXXPXXP motif (residues Arg368 to Pro374) and the F3 lobe are indicated by dashed lines and involve the side chains of Gln303 and Gln317 on the F3 lobe. C, details of the interaction between the FAK autophosphorylation Tyr397 segment and the F1 lobe. Hydrogen bonds are indicated with dashed lines and involve the side chains of Glu403 with His41 and Ser54 bonds. Tyr397 is surface exposed and not phosphorylated in the structure.
 
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2006, 281, 252-259) copyright 2006.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21220115 P.J.Lupardus, G.Skiniotis, A.J.Rice, C.Thomas, S.Fischer, T.Walz, and K.C.Garcia (2011).
Structural snapshots of full-length Jak1, a transmembrane gp130/IL-6/IL-6Rα cytokine receptor complex, and the receptor-Jak1 holocomplex.
  Structure, 19, 45-55.  
20150896 B.T.Goult, M.Bouaouina, P.R.Elliott, N.Bate, B.Patel, A.R.Gingras, J.G.Grossmann, G.C.Roberts, D.A.Calderwood, D.R.Critchley, and I.L.Barsukov (2010).
Structure of a double ubiquitin-like domain in the talin head: a role in integrin activation.
  EMBO J, 29, 1069-1080.
PDB codes: 2kc1 2kc2 2kma
20001213 C.A.Lipinski, and J.C.Loftus (2010).
Targeting Pyk2 for therapeutic intervention.
  Expert Opin Ther Targets, 14, 95.  
20966971 M.C.Frame, H.Patel, B.Serrels, D.Lietha, and M.J.Eck (2010).
The FERM domain: organizing the structure and function of FAK.
  Nat Rev Mol Cell Biol, 11, 802-814.  
20947018 P.R.Elliott, B.T.Goult, P.M.Kopp, N.Bate, J.G.Grossmann, G.C.Roberts, D.R.Critchley, and I.L.Barsukov (2010).
The Structure of the talin head reveals a novel extended conformation of the FERM domain.
  Structure, 18, 1289-1299.
PDB code: 3ivf
19664602 D.Zheng, E.Kurenova, D.Ucar, V.Golubovskaya, A.Magis, D.Ostrov, W.G.Cance, and S.N.Hochwald (2009).
Targeting of the protein interaction site between FAK and IGF-1R.
  Biochem Biophys Res Commun, 388, 301-305.  
18297732 E.J.Cram, K.M.Fontanez, and J.E.Schwarzbauer (2008).
Functional characterization of KIN-32, the Caenorhabditis elegans homolog of focal adhesion kinase.
  Dev Dyn, 237, 837-846.  
  18677107 S.T.Lim, D.Mikolon, D.G.Stupack, and D.D.Schlaepfer (2008).
FERM control of FAK function: implications for cancer therapy.
  Cell Cycle, 7, 2306-2314.  
18989950 V.M.Golubovskaya, C.Nyberg, M.Zheng, F.Kweh, A.Magis, D.Ostrov, and W.G.Cance (2008).
A small molecule inhibitor, 1,2,4,5-benzenetetraamine tetrahydrochloride, targeting the y397 site of focal adhesion kinase decreases tumor growth.
  J Med Chem, 51, 7405-7416.  
18549812 V.Ossovskaya, S.T.Lim, N.Ota, D.D.Schlaepfer, and D.Ilic (2008).
FAK nuclear export signal sequences.
  FEBS Lett, 582, 2402-2406.  
17967873 X.Cai, D.Lietha, D.F.Ceccarelli, A.V.Karginov, Z.Rajfur, K.Jacobson, K.M.Hahn, M.J.Eck, and M.D.Schaller (2008).
Spatial and temporal regulation of focal adhesion kinase activity in living cells.
  Mol Cell Biol, 28, 201-214.  
17574028 D.Lietha, X.Cai, D.F.Ceccarelli, Y.Li, M.D.Schaller, and M.J.Eck (2007).
Structural basis for the autoinhibition of focal adhesion kinase.
  Cell, 129, 1177-1187.
PDB codes: 2j0j 2j0k 2j0l 2j0m
17134719 Q.Li, M.R.Nance, R.Kulikauskas, K.Nyberg, R.Fehon, P.A.Karplus, A.Bretscher, and J.J.Tesmer (2007).
Self-masking in an intact ERM-merlin protein: an active role for the central alpha-helical domain.
  J Mol Biol, 365, 1446-1459.
PDB codes: 2i1j 2i1k
16823799 B.D.Cox, M.Natarajan, M.R.Stettner, and C.L.Gladson (2006).
New concepts regarding focal adhesion kinase promotion of cell migration and proliferation.
  J Cell Biochem, 99, 35-52.  
16889663 J.M.Corsi, E.Rouer, J.A.Girault, and H.Enslen (2006).
Organization and post-transcriptional processing of focal adhesion kinase gene.
  BMC Genomics, 7, 198.  
  16582480 K.Kitano, F.Yusa, and T.Hakoshima (2006).
Structure of dimerized radixin FERM domain suggests a novel masking motif in C-terminal residues 295-304.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 62, 340-345.
PDB code: 2d2q
16919435 S.K.Mitra, and D.D.Schlaepfer (2006).
Integrin-regulated FAK-Src signaling in normal and cancer cells.
  Curr Opin Cell Biol, 18, 516-523.  
16782899 S.Y.Chen, and H.C.Chen (2006).
Direct interaction of focal adhesion kinase (FAK) with Met is required for FAK to promote hepatocyte growth factor-induced cell invasion.
  Mol Cell Biol, 26, 5155-5167.  
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.

 

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