Bet3 in Golgi localization of tethering factor TRAPP
Mus musculus (house mouse)
Transport of proteins and other macromolecules across the cell membrane is a complex process. Proteins that have to be exported to the outside of the cell are synthetised in a special compartment called the endoplasmic reticulum, or simply ER. First, ribosomes build peptide chains which are then inserted into the ER. There they are packaged into vesicles. These vesicles are passed to another cell organelle, the Golgi Complex or Golgi Apparatus. It is a stack of flat, 1 micrometer wide disk-like compartments, attached to the cell membrane. The ER-to-Golgi vesicles bringing the proteins fuse with the Golgi reticulum. Inside the compartments the proteins are subject to further modifications. Some of them are successively shipped across to the opposite side of Golgi. There they are either released for incorporation into the cell membrane, or repackaged for transfer across the membrane into the cell exterior. The way the Golgi reticulum works is not very well understood.
The molecule presented here, Bet3p, is one of the components of the Transport Protein Particle (TRAPP) - a multiprotein complex that plays a crucial role in the transport of peptides to and across Golgi. The structure of Bet3p gives some hints about possible mechanisms for localization of TRAPP to Golgi. The fold comprises four alpha-helices and five beta-strands. There are two unusual features that become apparent after a close look at the molecule. One is the flat and positively charged surface. The charges come from 7 basic Arg and Lys residues per subunit. Such a surface would be the prefect 'magnet' to help Bet3p to attach itself to the cell membrane by electrostatic interactions with the negatively charged heads of the lipids forming the membrane bilayer. Residues Lys13 and Lys84 are shown to be crucial for the attachment process. The second unusual feature is a central hydrophobic channel constructed from helices alpha2, alpha3 and alpha4. It is narrow and penetrates deep into the protein interior. The hydrophobic properties of the channel make it an excellent anchor point for a hydrocarbon molecule. These features can explain the way Bet3p recognizes Golgi membranes. The flat charged surface pulls the complex onto the cell membrane. The interactions between this surface and the membrane are not strong enough to keep it static, and the complex is able to explore dynamically the two-dimensional lipid bilayer until it finds the appropriate hydrocarbon moiety. The latter then sticks into the hydrophobic channel cavity and anchors Bet3p to the cell wall. It is supposed that Golgi membranes are rich in such 'anchor chains' , and that it is how TRAPP complexes recognize them. It is still unclear though whether TRAPP assembles before or after attachment to the membrane. It is also possible that Bet3p is able to bind regardless of the presence of other TRAPP subunits.
Protein Data Bank (PDB)
Kim, Y.-G. Sohn, E.J. Seo, J. Lee, K.-J. Lee, H.-S. Hwang, I. Whiteway, M. Sacher, M. Oh, B.-H.; "Crystal Structure of Bet3 Reveals a Novel Mechanism for Golgi Localization of Tethering Factor Trapp"; Nature Struct. Biol.; (2005) 12:38-45 PubMed:15608655.
author: Rossen Apostolov