PDBsum entry 1wc8

Transport protein

PDB id: 1wc8

Contents

Protein chain

164 a.a. *

Ligands

MYR

Waters ×67

* Residue conservation analysis

PDB id:

1wc8

Name:

Transport protein

Title:

The crystal structure of mouse bet3p

Structure:

Trafficking protein particle complex subunit3. Chain: a. Synonym: bet3 homolog, bet3p. Engineered: yes

Source:

Mus musculus. Mouse. Organism_taxid: 10090. Expressed in: escherichia coli. Expression_system_taxid: 469008.

Biol. unit:

Dimer (from PDB file)

Resolution:

1.90Å R-factor: 0.217 R-free: 0.260

Authors:

Y.-G.Kim,M.Sacher,B.-H.Oh

Key ref:

Y.G.Kim et al. (2005). Crystal structure of bet3 reveals a novel mechanism for Golgi localization of tethering factor TRAPP. Nat Struct Mol Biol, 12, 38-45. PubMed id: 15608655 DOI: 10.1038/nsmb871

Date:

10-Nov-04 Release date: 13-Dec-04

Protein chain

O55013  (TPPC3_MOUSE) -  Trafficking protein particle complex subunit 3 from Mus musculus

Seq: 180 a.a.

Struc: 164 a.a.

DOI no: 10.1038/nsmb871

Nat Struct Mol Biol 12:38-45 (2005)

PubMed id: 15608655

Crystal structure of bet3 reveals a novel mechanism for Golgi localization of tethering factor TRAPP.

Y.G.Kim, E.J.Sohn, J.Seo, K.J.Lee, H.S.Lee, I.Hwang, M.Whiteway, M.Sacher, B.H.Oh.

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.

Selected figure(s)

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.

Figures were selected by an automated process.