Summary: Clathrin light chain
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Clathrin Edit Wikipedia article
| clathrin, light polypeptide (Lca) | |
|---|---|
| Identifiers | |
| Symbol | CLTA |
| Entrez | 1211 |
| HUGO | 2090 |
| OMIM | 118960 |
| RefSeq | NM_007096 |
| UniProt | P09496 |
| Other data | |
| Locus | Chr. 12 q23-q24 |
| clathrin, light polypeptide (Lcb) | |
|---|---|
| Identifiers | |
| Symbol | CLTB |
| Entrez | 1212 |
| HUGO | 2091 |
| OMIM | 118970 |
| RefSeq | NM_001834 |
| UniProt | P09497 |
| Other data | |
| Locus | Chr. 4 q |
| Clathrin light chain | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||
| Symbol | Clathrin_lg_ch | ||||||||
| Pfam | PF01086 | ||||||||
| InterPro | IPR000996 | ||||||||
| PROSITE | PDOC00196 | ||||||||
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| clathrin, heavy polypeptide (Hc) | |
|---|---|
| Identifiers | |
| Symbol | CLTC |
| Alt. symbols | CLTCL2 |
| Entrez | 1213 |
| HUGO | 2092 |
| OMIM | 118955 |
| RefSeq | NM_004859 |
| UniProt | Q00610 |
| Other data | |
| Locus | Chr. 17 q11-qter |
| clathrin, heavy polypeptide-like 1 | |
|---|---|
| Identifiers | |
| Symbol | CLTCL1 |
| Alt. symbols | CLTCL |
| Entrez | 8218 |
| HUGO | 2093 |
| OMIM | 601273 |
| RefSeq | NM_001835 |
| UniProt | P53675 |
| Other data | |
| Locus | Chr. 22 q11.2 |
| Clathrin propeller repeat | |||||||||
|---|---|---|---|---|---|---|---|---|---|
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| clathrin terminal domain complexed with tlpwdlwtt | |||||||||
| Identifiers | |||||||||
| Symbol | Clathrin_propel | ||||||||
| Pfam | PF01394 | ||||||||
| Pfam clan | CL0020 | ||||||||
| InterPro | IPR022365 | ||||||||
| SCOP | 1bpo | ||||||||
| SUPERFAMILY | 1bpo | ||||||||
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| Clathrin heavy-chain linker | |||||||||
|---|---|---|---|---|---|---|---|---|---|
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| clathrin terminal domain complexed with tlpwdlwtt | |||||||||
| Identifiers | |||||||||
| Symbol | Clathrin-link | ||||||||
| Pfam | PF09268 | ||||||||
| Pfam clan | CL0020 | ||||||||
| InterPro | IPR015348 | ||||||||
| SCOP | 1utc | ||||||||
| SUPERFAMILY | 1utc | ||||||||
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Clathrin is a protein that plays a major role in the formation of coated vesicles. Clathrin was first isolated and named by Barbara Pearse in 1975.[1] It forms a triskelion shape composed of three clathrin heavy chains and three light chains. When the triskelia interact they form a polyhedral lattice that surrounds the vesicle. Coat-proteins, like clathrin, are used to build small vesicles in order to safely transport molecules within and between cells. The endocytosis and exocytosis of vesicles allows cells to transfer nutrients, to import signaling receptors, to mediate an immune response after sampling the extracellular world, and to clean up the cell debris left by tissue inflammation. On occasion, this mechanism also provides a pathway for raiding pathogens or toxins.
Contents |
[edit] Structure
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The clathrin triskelion is composed of three clathrin heavy chains and three light chains interacting at their C-termini. The three heavy chains provide the structural backbone of the clathrin lattice, and the three light chains are thought to regulate the formation and disassembly of a clathrin lattice. Clathrin heavy chain is, in concept, broken down into multiple subdomains, starting with the N-terminal domain, followed by the ankle, distal leg, knee, proximal leg, and trimerization domains. The N-terminal domain consists of a seven-bladed β-propeller structure. The other domains form a super-helix of short alpha helices. This was originally determined from the structure of the proximal leg domain that identified and is composed of a smaller structural module referred to as clathrin heavy chain repeat motifs. The light chains bind primarily to the proximal leg portion of the heavy chain with some interaction near the trimerization domain. When triskelia assemble together in solution, they can interact with enough flexibility to form 6-sided rings that yield a flatter lattice, or 5-sided rings that are necessary for curved lattice formation. When many triskelions connect, they can form a basket-like structure.
The structure shown above, is built of 36 triskelia, one of which is highlighted in green. When triskelia snap together in solution, they can interact with enough flexibility to form either 6-sided rings that yield a flatter surface or 5-sided rings with higher curvature. In a cell, a triskelion floating in the cytoplasm binds to an adaptor protein (shown on the next page), linking one of its three feet to the membrane at a time. This triskelion will bind to other membrane-attached triskelia to form a rounded lattice of hexagons and pentagons, reminiscent of the panels on a soccer ball, that pulls the membrane into a bud. By constructing different combinations of 5-sided and 6-sided rings, vesicles of different sizes may assemble. The structure shown here represents the second-smallest possible cage structure, which is actually too small to contain a functional vesicle. It was created in the laboratory by reconstituting triskelions without a lipid vesicle. The smallest clathrin cage commonly photographed, called a mini-coat, has 12 pentagons and only two hexagons. Even smaller cages with zero hexagons probably do not form from the native protein, because the feet of the triskelia are too bulky.
[edit] Function
Like many proteins, clathrin represents a perfect case of form following function; it performs critical roles in shaping rounded vesicles in the cytoplasm for intracellular trafficking. Clathrin-coated vesicles (CCV) selectively sort cargo at the cell membrane, trans-Golgi network, and endosomal compartments for multiple membrane traffic pathways. After a vesicle buds into the cytoplasm, the coat rapidly disassembles, allowing the clathrin to recycle while the vesicle gets transported to a variety of locations. Adaptor molecules are responsible for self-assembly and recruitment. Two examples of adaptor proteins are AP180[2] and epsin.[3][4][5] AP180 is used in synaptic vesicle formation. It recruits clathrin to membranes and also promotes its polymerization. Epsin also recruits clathrin to membranes and promotes its polymerization, and can help deform the membrane, and thus clathrin-coated vesicles can bud. In a cell, a triskelion floating in the cytoplasm binds to an adaptor protein, linking one of its feet to the membrane at a time. The skelion will bind to other ones attached to the membrane to form a polyhedral lattice, skelion, which pulls the membrane into a bud. The skelion does not bind directly to the membrane, but binds to the adaptor proteins that recognize the molecules on the membrane surface.
Clathrin has another function aside from the coating of organelles. In non-dividing cells, the formation of clathrin-coated vesicles occurs continuously. Formation of clathrin-coated vesicles is shut down in cells undergoing mitosis. During mitosis, clathrin binds to the spindle apparatus. Clathrin aids in the congression of chromosomes by stabilizing fibres of the mitotic spindle. Clathrin is bound directly through the amino-terminal domain of the clathrin heavy chain. During mitosis the clathrin binds directly to the microtubules or microtubule-associated proteins. The stabilization of kinetochore fibres requires the trimetric structure of clathrin in order to strengthen the spindle fibres.[6]
Clathrin-mediated endocytosis (CME) regulates many cellular physiological processes such as the internalization of growth factors and receptors, entry of pathogens, and synaptic transmission. It is believed that cellular invaders use the nutrient pathway to gain access to a cell's replicating mechanisms. Certain signalling molecules open the nutrients pathway. Two chemical compounds called Pitstop 1 and Pitstop 2, selective clathrin inhibitors, can interfere with the pathogenic activity, and thus protect the cells against invasion. These two compounds selectively block the endocytic ligand association with the clathrin terminal domain.[7]
[edit] See also
[edit] References
- ^ Pearse BM (April 1976). "Clathrin: a unique protein associated with intracellular transfer of membrane by coated vesicles". Proceedings of the National Academy of Sciences of the United States of America 73 (4): 1255â9. doi:10.1073/pnas.73.4.1255. PMC 430241. PMID 1063406. //www.ncbi.nlm.nih.gov/pmc/articles/PMC430241/.
- ^ McMahon HT. "Clathrin and its interactions with AP180.". MRC Laboratory of Molecular Biology. http://www.endocytosis.org/AP180/Clathrin.html. Retrieved 2009-04-17. "micrographs of clathrin assembly"
- ^ McMahon HT. "Epsin 1 EM gallery". MRC Laboratory of Molecular Biology,. http://www.endocytosis.org/epsin/EM/MonolayerEMs.html. Retrieved 2009-04-17. "micrographs of vesicle budding"
- ^ Ford MG, Pearse BM, Higgins MK, Vallis Y, Owen DJ, Gibson A, Hopkins CR, Evans PR, McMahon HT (February 2001). "Simultaneous binding of PtdIns(4,5)P2 and clathrin by AP180 in the nucleation of clathrin lattices on membranes". Science 291 (5506): 1051â5. doi:10.1126/science.291.5506.1051. PMID 11161218. http://www.endocytosis.org/epsin/EM/ford.pdf.
- ^ Higgins MK, McMahon HT (May 2002). "Snap-shots of clathrin-mediated endocytosis". Trends in Biochemical Sciences 27 (5): 257â63. doi:10.1016/S0968-0004(02)02089-3. PMID 12076538. http://www.endocytosis.org/epsin/EM/mcmahon.pdf.
- ^ Royle SJ, Bright NA, Lagnado L (April 2005). "Clathrin is required for the function of the mitotic spindle". Nature 434 (7037): 1152â1157. doi:10.1038/nature03502. PMID 15858577. http://www.nature.com/nature/journal/v434/n7037/full/nature03502.html.
- ^ Role of the Clathrin Terminal Domain in Regulating Coated Pit Dynamics Revealed by Small Molecule Inhibition|Cell, Volume 146, Issue 3, 471-484, 5 August 2011 Abstract
[edit] Further reading
- Wakeham DE, Chen CY, Greene B, Hwang PK, Brodsky FM (October 2003). "Clathrin self-assembly involves coordinated weak interactions favorable for cellular regulation". The EMBO Journal 22 (19): 4980â90. doi:10.1093/emboj/cdg511. PMC 204494. PMID 14517237. //www.ncbi.nlm.nih.gov/pmc/articles/PMC204494/.
- Ford MG, Mills IG, Peter BJ, Vallis Y, Praefcke GJ, Evans PR, McMahon HT (September 2002). "Curvature of clathrin-coated pits driven by epsin". Nature 419 (6905): 361â6. doi:10.1038/nature01020. PMID 12353027.
- Fotin A, Cheng Y, Sliz P, Grigorieff N, Harrison SC, Kirchhausen T, Walz T (December 2004). "Molecular model for a complete clathrin lattice from electron cryomicroscopy". Nature 432 (7017): 573â9. doi:10.1038/nature03079. PMID 15502812.
- Mousavi SA, Malerød L, Berg T, Kjeken R (January 2004). "Clathrin-dependent endocytosis". The Biochemical Journal 377 (Pt 1): 1â16. doi:10.1042/BJ20031000. PMC 1223844. PMID 14505490. //www.ncbi.nlm.nih.gov/pmc/articles/PMC1223844/.
- Smith CJ, Grigorieff N, Pearse BM (September 1998). "Clathrin coats at 21 A resolution: a cellular assembly designed to recycle multiple membrane receptors". The EMBO Journal 17 (17): 4943â53. doi:10.1093/emboj/17.17.4943. PMC 1170823. PMID 9724631. //www.ncbi.nlm.nih.gov/pmc/articles/PMC1170823/. (Model of Clathrin assembly)
- Pérez-Gómez J, Moore I (March 2007). "Plant endocytosis: it is clathrin after all". Current Biology : CB 17 (6): R217â9. doi:10.1016/j.cub.2007.01.045. PMID 17371763. (Review on involvement of clathrin in plant endocytosis - proven recently)
- Royle SJ, Bright NA, Lagnado L (April 2005). "Clathrin is required for the function of the mitotic spindle". Nature 434 (7037): 1152â7. doi:10.1038/nature03502. PMID 15858577.
- Knuehl C, Chen CY, Manalo V, Hwang PK, Ota N, Brodsky FM (December 2006). "Novel binding sites on clathrin and adaptors regulate distinct aspects of coat assembly". Traffic (Copenhagen, Denmark) 7 (12): 1688â700. doi:10.1111/j.1600-0854.2006.00499.x. PMID 17052248.
- Edeling MA, Smith C, Owen D (January 2006). "Life of a clathrin coat: insights from clathrin and AP structures". Nature Reviews Molecular Cell Biology 7 (1): 32â44. doi:10.1038/nrm1786. PMID 16493411.
[edit] External links
- Eukaryotic Linear Motif resource motif class LIG_Clathr_ClatBox_1.html LIG_Clathr_ClatBox_1
- Eukaryotic Linear Motif resource motif class LIG_Clathr_ClatBox_2.html LIG_Clathr_ClatBox_2
- Clathrin structure
- Membrane Dynamics
- Clathrin Dynamics ASCB Image & Video Library
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This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.
Clathrin light chain Provide feedback
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External database links
| PANDIT: | PF01086 |
| PROSITE: | PDOC00196 |
| Pseudofam: | PF01086 |
| SYSTERS: | Clathrin_lg_ch |
This tab holds annotation information from the InterPro database.
InterPro entry IPR000996
Proteins synthesized on the ribosome and processed in the endoplasmic reticulum are transported from the Golgi apparatus to the trans-Golgi network (TGN), and from there via small carrier vesicles to their final destination compartment. These vesicles have specific coat proteins (such as clathrin or coatomer) that are important for cargo selection and direction of transport [PUBMED:15261670]. Clathrin coats contain both clathrin (acts as a scaffold) and adaptor complexes that link clathrin to receptors in coated vesicles. Clathrin-associated protein complexes are believed to interact with the cytoplasmic tails of membrane proteins, leading to their selection and concentration. The two major types of clathrin adaptor complexes are the heterotetrameric adaptor protein (AP) complexes, and the monomeric GGA (Golgi-localising, Gamma-adaptin ear domain homology, ARF-binding proteins) adaptors [PUBMED:17449236, PUBMED:11598180].
Clathrin is a trimer composed of three heavy chains and three light chains, each monomer projecting outwards like a leg; this three-legged structure is known as a triskelion [PUBMED:15752139, PUBMED:16806884]. The heavy chains form the legs, their N-terminal beta-propeller regions extending outwards, while their C-terminal alpha-alpha-superhelical regions form the central hub of the triskelion. Peptide motifs can bind between the beta-propeller blades. The light chains appear to have a regulatory role, and may help orient the assembly and disassembly of clathrin coats as they interact with hsc70 uncoating ATPase [PUBMED:16734666]. Clathrin triskelia self-polymerise into a curved lattice by twisting individual legs together. The clathrin lattice forms around a vesicle as it buds from the TGN, plasma membrane or endosomes, acting to stabilise the vesicle and facilitate the budding process [PUBMED:15261670]. The multiple blades created when the triskelia polymerise are involved in multiple protein interactions, enabling the recruitment of different cargo adaptors and membrane attachment proteins [PUBMED:16699812].
This entry represents clathrin light chains, which are more divergent in sequence than the heavy chains [PUBMED:14617352]. In higher eukaryotes, two genes encode distinct but related light chains, each of which can yield two separate forms via alternative splicing. In yeast there is a single light chain whose sequence is only distantly related to that of higher eukaryotes. Clathrin light chains have a conserved acidic N-terminal domain, a central coiled-coil domain and a conserved C-terminal domain.
More information about these proteins can be found at Protein of the Month: Clathrin [PUBMED:].
Gene Ontology
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
| Cellular component | clathrin coat of coated pit (GO:0030132) |
| clathrin coat of trans-Golgi network vesicle (GO:0030130) | |
| Molecular function | structural molecule activity (GO:0005198) |
| Biological process | intracellular protein transport (GO:0006886) |
| vesicle-mediated transport (GO:0016192) |
Domain organisation
Below is a listing of the unique domain organisations or architectures in which this domain is found. More...
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Alignments
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| Seed (28) |
Full (493) |
Representative proteomes | NCBI (500) |
Meta (3) |
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| RP15 (94) |
RP35 (157) |
RP55 (232) |
RP75 (289) |
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| PP/heatmap | 1 | |||||||
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| Seed (28) |
Full (493) |
Representative proteomes | NCBI (500) |
Meta (3) |
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|---|---|---|---|---|---|---|---|---|
| RP15 (94) |
RP35 (157) |
RP55 (232) |
RP75 (289) |
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| Raw Stockholm | ||||||||
| Gzipped | ||||||||
You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.
External links
MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER3.
HMM logo
HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...
Trees
This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.
Note: You can also download the data file for the tree.
Curation and family details
This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.
Curation
| Seed source: | Prosite |
| Previous IDs: | none |
| Type: | Family |
| Author: | Finn RD, Bateman A |
| Number in seed: | 28 |
| Number in full: | 493 |
| Average length of the domain: | 200.20 aa |
| Average identity of full alignment: | 27 % |
| Average coverage of the sequence by the domain: | 86.99 % |
HMM information
| HMM build commands: |
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
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| Model details: |
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| Model length: | 225 | ||||||||||||
| Family (HMM) version: | 12 | ||||||||||||
| Download: | download the raw HMM for this family |
Species distribution
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Structures
For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the Clathrin_lg_ch domain has been found. There are 6 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.
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