TRAPP complex
Encyclopedia
TRAPP is a protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...

 involved in particle transport between organelle
Organelle
In cell biology, an organelle is a specialized subunit within a cell that has a specific function, and is usually separately enclosed within its own lipid bilayer....

s.

Protein folding and the Endoplasmic Reticulum (ER)

Protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...

s that are destined for the plasma membrane or export to the extracellular environment in eukaryotic cells are translated on ribosome
Ribosome
A ribosome is a component of cells that assembles the twenty specific amino acid molecules to form the particular protein molecule determined by the nucleotide sequence of an RNA molecule....

s that sit on the rough endoplasmic reticulum
Endoplasmic reticulum
The endoplasmic reticulum is an organelle of cells in eukaryotic organisms that forms an interconnected network of tubules, vesicles, and cisternae...

 (RER). Most proteins are co-translationally transported into the ER (i.e., while the ribosome
Ribosome
A ribosome is a component of cells that assembles the twenty specific amino acid molecules to form the particular protein molecule determined by the nucleotide sequence of an RNA molecule....

 is translating the mRNA code into a polypeptide code, the polypeptide is simultaneously inserted via the "translocon
Translocon
The translocon is the complex of proteins associated with the translocation of nascent polypeptides across membranes. In eukaryotes the polypeptides are transported into the interior space of the endoplasmic reticulum from the cytosol...

pore" into the ER). The ER provides an environment that helps these nascent polypeptides fold into and become functional or partially functional proteins. The ER provides an oxidizing environment (for formation of disulfide bonds) and the necessary chaperones (folding assisting agents that are not part of the final protein) that help in polypeptide folding. Numerous exported proteins form disulfide bonds
Disulfide
In chemistry, a disulfide usually refers to the structural unit composed of a linked pair of sulfur atoms. Disulfide usually refer to a chemical compound that contains a disulfide bond, such as diphenyl disulfide, C6H5S-SC6H5....

 as these covalent bonds stabilize the protein structure in harsh extracellular environments (a classical example are antibodies which are secreted by B-cell of our immune system
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...

, the heavy and light chain polypeptide of antibodies are held together via disulfide bonds). Another key event that takes place in the ER is called N-linked glycosylation
Glycosylation
Glycosylation is the reaction in which a carbohydrate, i.e. a glycosyl donor, is attached to a hydroxyl or other functional group of another molecule . In biology glycosylation refers to the enzymatic process that attaches glycans to proteins, lipids, or other organic molecules...

. In this process, polypeptides that have a unique stretch of 3 amino acids (Asparagine - X - Serine/threonine, where X represents any amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...

 except proline
Proline
Proline is an α-amino acid, one of the twenty DNA-encoded amino acids. Its codons are CCU, CCC, CCA, and CCG. It is not an essential amino acid, which means that the human body can synthesize it. It is unique among the 20 protein-forming amino acids in that the α-amino group is secondary...

), the amide group of asparagine is modified with a complex sugar moiety. Other types of glycosylations found include S-linked (via cysteine residues), C-linked (via tryptophan) and O-linked (via serine or threonine). By far, N-linked glycosylation is the most abundant post-translational modification found in eukaryotic cells.

Protein export form the ER and the COP II coat

Once proteins have folded and are ready to be transported out of the ER it is thought that they assemble at specific site within the ER called "ER exit sites". These sites can be transient but are most likely situated in the ER where the ER is close to the next transport compartment, the vesicular-tubular cluster
Vesicular-tubular cluster
A vesicular-tubular cluster , also referred to as the ER-Golgi intermediate compartment , is an organelle in eukaryotic cells. This compartment mediates trafficking between the endoplasmic reticulum and Golgi complex, facilitating the sorting of cargo...

 (VTC) (also referred to as the ER-Golgi Intermediate Compartment (ERGIC)). The details of how proteins are concentrated or localized to the exit site is unclear (some aspects are emerging!) but the actual process of budding
Budding
Budding is a form of asexual reproduction in which a new organism grows on another one. The new organism remains attached as it grows, separating from the parent organism only when it is mature. Since the reproduction is asexual, the newly created organism is a clone and is genetically identical...

 a vesicle
Vesicle (biology)
A vesicle is a bubble of liquid within another liquid, a supramolecular assembly made up of many different molecules. More technically, a vesicle is a small membrane-enclosed sack that can store or transport substances. Vesicles can form naturally because of the properties of lipid membranes , or...

 containing these proteins start with a protein called Sec12. This protein recruits a small GTPase
GTPase
GTPases are a large family of hydrolase enzymes that can bind and hydrolyze guanosine triphosphate . The GTP binding and hydrolysis takes place in the highly conserved G domain common to all GTPases.-Functions:...

 called Sar1
Sar1
SAR1A or Sar1 is a protein involved in membrane trafficking. It is a GTPase found in COPII vesicles. It regulates the assembly and disassembly of COPII coats....

 (think of Sar1 as a switch, it is active when bound to GTP
Guanosine triphosphate
Guanosine-5'-triphosphate is a purine nucleoside triphosphate. It can act as a substrate for the synthesis of RNA during the transcription process...

 and inactive when it hydrolyses the GTP to GDP
Guanosine diphosphate
Guanosine diphosphate, abbreviated GDP, is a nucleoside diphosphate. It is an ester of pyrophosphoric acid with the nucleoside guanosine. GDP consists of the pyrophosphate group, the pentose sugar ribose, and the nucleobase guanine....

). This in turn leads to the recruitment of a protein complex, the Sec23/Sec24 and the Sec13/Sec31 complex (also known as the COPII
COPII
COPII is a type of vesicle coat protein that transports proteins from the rough endoplasmic reticulum to the Golgi apparatus. This is termed anterograde transport. The name "COPII" refers to the specific coat protein complex that initiates the budding process...

 coat). In a nutshell what these proteins do is form a mesh at the ER exit site and the mesh through mechanical curvature forms a little "blob" that pinches off from the ER with proteins inside (think, playdough as the ER and your hand as the Sec complex pinching off little bits). The mesh disassembles off the budded vesicle when Sar1 hydrolyses the GTP to GDP. Interestingly, this activity of Sar1 is enhanced by Sec23/24.

Vesicle transport and tethering

Once the vesicles pinch off from the ER they are transported passively (by diffusion
Diffusion
Molecular diffusion, often called simply diffusion, is the thermal motion of all particles at temperatures above absolute zero. The rate of this movement is a function of temperature, viscosity of the fluid and the size of the particles...

) or actively (by little intracellular motors that run on cytoskeletal tracks). The mode of transport
Mode of transport
Mode of transport is a term used to distinguish substantially different ways to perform transport. The most dominant modes of transport are aviation, land transport, which includes rail, road and off-road transport, and ship transport...

 seems to be influenced by distance. Short distances may tend towards passive transport whereas longer distances tend towards active transport
Dynein
Dynein is a motor protein in cells which converts the chemical energy contained in ATP into the mechanical energy of movement. Dynein transports various cellular cargo by "walking" along cytoskeletal microtubules towards the minus-end of the microtubule, which is usually oriented towards the cell...

. Once these vesicles reach their destination they need to be first physically linked with their acceptor compartment (else they may float away!!). This process is facilitated by "tether
Tether
A tether is a cord, fixture, or signal that anchors something movable to a reference point which may be fixed or moving. There are a number of applications for tethers: balloons, kites, tethered wind-energy conversion systems, anchors, tethered water-flow energy conversion systems, towing, animal...

s". Tethers come in two "flavors" long protein(s) with domains called "coiled-coil
Coiled coil
A coiled coil is a structural motif in proteins, in which 2-7 alpha-helices are coiled together like the strands of a rope . Many coiled coil type proteins are involved in important biological functions such as the regulation of gene expression e.g. transcription factors...

" or complexes
Protein complex
A multiprotein complex is a group of two or more associated polypeptide chains. If the different polypeptide chains contain different protein domain, the resulting multiprotein complex can have multiple catalytic functions...

 of many subunits which are for the most part globular
Globular protein
Globular proteins, or spheroproteins are one of the two main protein classes, comprising "globe"-like proteins that are more or less soluble in aqueous solutions...

. The tether that functions to "tether" ER derived vesicles to the VTC (or golgi
Golgi
Golgi may refer to:*Camillo Golgi , Italian physician and scientist after which the following terms are named:**Golgi apparatus , an organelle in the eukaryotic cell...

 in case of lower eukaryotes), the next compartment in the transport pathway is called Transport Protein Particle (TRAPP).

TRAPP as a tether

TRAPP also comes in two "flavors", TRAPP I & II. TRAPP I is a multisubunit complex that consists of seven subunits (Bet5, Bet3, Trs20, Trs23, Trs31, Trs33, Trs85). TRAPPII has three additional subunits (Trs65, Trs120 and Trs130) and functions as a tether at latter stages of the transport pathway. TRAPP I binds these ER derived vesicles and brings the vesicle closer to the acceptor membrane. This close juxtapositioning of the two membranes allows the interaction between SNARE
Snare
Snare may refer to:* Snare trap, a kind of trap used for capturing animals* Snare drum* SNARE , a family of proteins involved in vesicle fusion* The Snares, a group of islands approximately 200 kilometres south of New Zealand...

's (soluble NSF (N-ethylmaleimide sensitive Factor) attachment protein receptor) on both compartments. The interacting SNARE's then pull the membranes close and allow for fusion.

A recent report has shown that the initial interaction between TRAPP and the ER derived vesicle is mediated via the interaction between the TRAPP subunit Bet3 and the COPII coat subunit, Sec23. The conventional view of tethering/fusion assumed that the vesicle coat is shed prior to tethering and fusion but this report argues for a model where the initial tethering step takes place on a coated or partially coated vesicle. The TRAPPI complex minus the subunit Trs85 was recently crystallized as two subcomplexes that were then modelled on EM etch data to reveal a possible crystal structure for the entire complex. A putative ypt/rab binding site was indicated on the crystal structure involving the subunits Trs23 and Bet5. Incidentally, all 5 essential small subunits (Trs31, Trs20, Bet3, Bet5 and Trs23) are required to reconstitute efficient exchange activity on ypt1 in vitro. Therefore, it remains to be seen whether the interface between ypt1 and TRAPPI is only confined to Trs23 and Bet5 and how the other subunit influence exchange activity.

Further reading

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