PDBsum entry 1b0x

Transferase

PDB id: 1b0x

Contents

Protein chain

72 a.a. *

Waters ×53

* Residue conservation analysis

PDB id:

1b0x

Name:

Transferase

Title:

The crystal structure of an eph receptor sam domain reveals a mechanism for modular dimerization.

Structure:

Protein (epha4 receptor tyrosine kinase). Chain: a. Fragment: sam domain. Engineered: yes

Source:

Mus musculus. House mouse. Organism_taxid: 10090. Strain: bl21. Expressed in: escherichia coli. Expression_system_taxid: 562.

Biol. unit:

Dimer (from PDB file)

Resolution:

2.00Å R-factor: 0.229 R-free: 0.278

Authors:

D.Stapleton,I.Balan,T.Pawson,F.Sicheri

Key ref:

D.Stapleton et al. (1999). The crystal structure of an Eph receptor SAM domain reveals a mechanism for modular dimerization. Nat Struct Biol, 6, 44-49. PubMed id: 9886291 DOI: 10.1038/4917

Date:

14-Nov-98 Release date: 03-May-99

Protein chain

Q03137  (EPHA4_MOUSE) -  Ephrin type-A receptor 4 from Mus musculus

Seq: 986 a.a.

Struc: 72 a.a.

Enzyme reactions

• Enzyme class: E.C.2.7.10.1 - receptor protein-tyrosine kinase.
• Reaction: 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: 10.1038/4917

Nat Struct Biol 6:44-49 (1999)

PubMed id: 9886291

The crystal structure of an Eph receptor SAM domain reveals a mechanism for modular dimerization.

D.Stapleton, I.Balan, T.Pawson, F.Sicheri.

ABSTRACT

The sterile alpha motif (SAM) domain is a novel protein module of approximately 70 amino acids that is found in a variety of signaling molecules including tyrosine and serine/threonine protein kinases, cytoplasmic scaffolding and adaptor proteins, regulators of lipid metabolism, and GTPases as well as members of the ETS family of transcription factors. The SAM domain can potentially function as a protein interaction module through the ability to homo- and hetero-oligomerize with other SAM domains. This functional property elicits the oncogenic activation of chimeric proteins arising from translocation of the SAM domain of TEL to coding regions of the betaPDGF receptor, Abl, JAK2 protein kinase and the AML1 transcription factor. Here we describe the 2.0 A X-ray crystal structure of a SAM domain homodimer from the intracellular region of the EphA4 receptor tyrosine kinase. The structure reveals a mode of dimerization that we predict is shared amongst the SAM domains of the Eph receptor tyrosine kinases and possibly other SAM domain containing proteins. These data indicate a mechanism through which an independently folding protein module can form homophilic complexes that regulate signaling events at the membrane and in the nucleus.

Selected figure(s)

Figure 2.
Figure 2. Ribbons depictions of the EphA4 receptor SAM domain homo−dimer. The SAM dimer is viewed a, down the two−fold symmetry axis and b, perpendicular to the symmetry axis. The dimer subunits are colored red and blue and −helices are labeled. c, Ribbons stereo view highlighting the dimer interface region. Aromatic, aliphatic, methionine, histidine and arginine interacting side chains are coloured light blue, green, yellow, orange, and blue (see Fig. 1 for residue identification). All ribbon diagrams were generated using RIBBONS^30.

Figure 3.
Figure 3. a,b, Molecular surface and worm representations of the SAM homodimer. The molecular surface of one subunit is shown with hydrophobic (Met, Val, Leu, Ile, Phe,), basic (Arg, Lys) and acidic (Glu, Asp) side chains colored green, blue and red, respectively. The two perspectives differ by a 90° rotation about the vertical axis. In (b) the two−fold rotation axis relating the two subunits of the dimer is shown. The buried surface area of the dimer interface is 1,923 Å^2. All molecular surfaces were generated using GRASP^1. c, Electron density in a simulated annealing^32 omit map computed at 2.0 Å and contoured at 1.5 . |2F[o] − F[c]| coefficients were used to calculate the map. Superimposed are the omitted residues Asp 918, Trp 919 and Leu 920 of the final EphA4 model.

The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Biol (1999, 6, 44-49) copyright 1999.

Figures were selected by the author.