 |
PDBsum entry 1wc8
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Transport protein
|
PDB id
|
|
|
|
1wc8
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
Crystal structure of bet3 reveals a novel mechanism for golgi localization of tethering factor trapp.
|
|
|
Authors
|
|
Y.G.Kim,
E.J.Sohn,
J.Seo,
K.J.Lee,
H.S.Lee,
I.Hwang,
M.Whiteway,
M.Sacher,
B.H.Oh.
|
|
|
Ref.
|
|
Nat Struct Mol Biol, 2005,
12,
38-45.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
Abstract
|
|
|
Transport protein particle (TRAPP) is a large multiprotein complex involved in
endoplasmic reticulum-to-Golgi and intra-Golgi traffic. TRAPP specifically and
persistently resides on Golgi membranes. Neither the mechanism of the
subcellular localization nor the function of any of the individual TRAPP
components is known. Here, the crystal structure of mouse Bet3p (bet3), a
conserved TRAPP component, reveals a dimeric structure with hydrophobic
channels. The channel entrances are located on a putative membrane-interacting
surface that is distinctively flat, wide and decorated with positively charged
residues. Charge-inversion mutations on the flat surface of the highly conserved
yeast Bet3p led to conditional lethality, incorrect localization and membrane
trafficking defects. A channel-blocking mutation led to similar defects. These
data delineate a molecular mechanism of Golgi-specific targeting and anchoring
of Bet3p involving the charged surface and insertion of a Golgi-specific
hydrophobic moiety into the channels. This essential subunit could then direct
other TRAPP components to the Golgi.
|
|
|
|
|
|
|
|
Figure 2.
Figure 2. Unusually flat surface of bet3. (a) Ribbon drawing
looking down the molecular two-fold axis, which runs
perpendicular to the orientation of bet3 in Figure 1a.
Myristoyl-Cys68 is a CPK model. The acidic or basic residues
exposed on the surface are in ball-and-stick form. The flexible
portion of loop  2-
3
is red. The coordinates of a completely disordered residue,
Arg67, should be considered unfixed. (b) Electrostatic surface
representation. The orientation of the molecule is the same as
in a. The positive and negative charges arising from the
indicated residues in a are in blue and red, respectively.
Circles, positions of the entryway to the channel on each
subunit. The two lysines substituted with glutamate (see text)
are labeled with bold yellow letters.
|
|
Figure 5.
Figure 5. Model for Golgi-specific targeting and localization of
TRAPP. The flat surface of mouse bet3, which is predominantly
positively charged, would interact with negatively charged polar
head groups of lipids. The landed bet3 protein could search for
its Golgi-specific partner protein in a two-dimensional fashion.
The secondary and firm attachment of bet3 to the Golgi occurs
via the insertion of the acyl chain of the partner protein into
the hydrophobic channel of bet3. In the beacon model, bet3 first
attaches to the Golgi and directs the recruitment of the other
TRAPP subunits. In the headlight model, the complex or a portion
of the complex is preassembled in the cytosol and directed to
the Golgi by the bet3 subunit. Secondary attachment to the Golgi
would occur via the acyl groups as described above. The
schematic drawing of the TRAPP complex does not reflect how
TRAPP components interact with each other in the complex, which
is as yet unknown.
|
|
|
|
|
|
The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nat Struct Mol Biol
(2005,
12,
38-45)
copyright 2005.
|
|
|
|
|
|
|
