PDBsum entry 3bs7

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protein Protein-protein interface(s) links
Signaling protein PDB id
Protein chains
75 a.a. *
Waters ×290
* Residue conservation analysis
PDB id:
Name: Signaling protein
Title: Crystal structure of the sterile alpha motif (sam) domain of hyphen/aveugle
Structure: Protein aveugle. Chain: a, b. Fragment: sterile alpha motif (sam) domain. Unp residues 21-98. Engineered: yes
Source: Drosophila melanogaster. Fruit fly. Organism_taxid: 7227. Gene: ave. Expressed in: escherichia coli. Expression_system_taxid: 562
1.90Å     R-factor:   0.217     R-free:   0.265
Authors: T.Rajakulendran,F.Sicheri
Key ref:
T.Rajakulendran et al. (2008). CNK and HYP form a discrete dimer by their SAM domains to mediate RAF kinase signaling. Proc Natl Acad Sci U S A, 105, 2836-2841. PubMed id: 18287031 DOI: 10.1073/pnas.0709705105
22-Dec-07     Release date:   26-Feb-08    
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Protein chains
Pfam   ArchSchema ?
Q8ML92  (AVE_DROME) -  Protein aveugle
106 a.a.
75 a.a.
Key:    PfamA domain  Secondary structure  CATH domain


DOI no: 10.1073/pnas.0709705105 Proc Natl Acad Sci U S A 105:2836-2841 (2008)
PubMed id: 18287031  
CNK and HYP form a discrete dimer by their SAM domains to mediate RAF kinase signaling.
T.Rajakulendran, M.Sahmi, I.Kurinov, M.Tyers, M.Therrien, F.Sicheri.
RAF kinase functions in the mitogen-activated protein kinase (MAPK) pathway to transmit growth signals to the downstream kinases MEK and ERK. Activation of RAF catalytic activity is facilitated by a regulatory complex comprising the proteins CNK (Connector enhancer of KSR), HYP (Hyphen), and KSR (Kinase Suppressor of Ras). The sterile alpha-motif (SAM) domain found in both CNK and HYP plays an essential role in complex formation. Here, we have determined the x-ray crystal structure of the SAM domain of CNK in complex with the SAM domain of HYP. The structure reveals a single-junction SAM domain dimer of 1:1 stoichiometry in which the binding mode is a variation of polymeric SAM domain interactions. Through in vitro and in vivo mutational analyses, we show that the specific mode of dimerization revealed by the crystal structure is essential for RAF signaling and facilitates the recruitment of KSR to form the CNK/HYP/KSR regulatory complex. We present two docking-site models to account for how SAM domain dimerization might influence the formation of a higher-order CNK/HYP/KSR complex.
  Selected figure(s)  
Figure 1.
The SAM domains of CNK and HYP interact directly. (A) Domain architecture of CNK and HYP. CNK is characterized by the presence of a SAM (sterile α-motif) domain; a CRIC (conserved region in CNK); a PDZ (PSD-95, ZO-1/2, Dlg-1) domain; and a PH (pleckstrin homology) domain. HYP contains a single SAM domain. Indicated protein sizes correspond to the Drosophila members. (B) Pull-down analysis of GST-dHYP^SAM with hCNK2^SAM. GST and GST-Vts1^SAM served as controls.
Figure 3.
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20820846 C.M.Udell, T.Rajakulendran, F.Sicheri, and M.Therrien (2011).
Mechanistic principles of RAF kinase signaling.
  Cell Mol Life Sci, 68, 553-565.  
20008569 J.Ding, O.Tchaicheeyan, and L.Ambrosio (2010).
Drosophila Raf's N terminus contains a novel conserved region and can contribute to torso RTK signaling.
  Genetics, 184, 717-729.  
20634316 J.Lim, M.Zhou, T.D.Veenstra, and D.K.Morrison (2010).
The CNK1 scaffold binds cytohesins and promotes insulin pathway signaling.
  Genes Dev, 24, 1496-1506.  
20017116 R.L.Rich, and D.G.Myszka (2010).
Grading the commercial optical biosensor literature-Class of 2008: 'The Mighty Binders'.
  J Mol Recognit, 23, 1.  
19765305 M.Leone, J.Cellitti, and M.Pellecchia (2009).
The Sam domain of the lipid phosphatase Ship2 adopts a common model to interact with Arap3-Sam and EphA2-Sam.
  BMC Struct Biol, 9, 59.
PDB code: 2kg5
18991394 M.Leone, J.Cellitti, and M.Pellecchia (2008).
NMR studies of a heterotypic Sam-Sam domain association: the interaction between the lipid phosphatase Ship2 and the EphA2 receptor.
  Biochemistry, 47, 12721-12728.
PDB code: 2k4p
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