 |
PDBsum entry 1b0x
|
|
|
|
|
 |
Contents |
 |
|
|
|
|
|
|
|
|
|
|
* Residue conservation analysis
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
The crystal structure of an eph receptor sam domain reveals a mechanism for modular dimerization.
|
|
|
Authors
|
|
D.Stapleton,
I.Balan,
T.Pawson,
F.Sicheri.
|
|
|
Ref.
|
|
Nat Struct Biol, 1999,
6,
44-49.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
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.
|
|
|
|
|
|
|
|
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.
|
|
|
|
|
|
|
