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39  structures 177  species 2  interactions 581  sequences 30  architectures

Family: Clathrin_propel (PF01394)

Summary: Clathrin propeller repeat

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This is the Wikipedia entry entitled "Clathrin". More...

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
Clathrin coat structure
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
Mechanism of clathrin-dependent endocytosis.
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
PDB 1utc EBI.jpg
clathrin terminal domain complexed with tlpwdlwtt
Identifiers
Symbol Clathrin_propel
Pfam PF01394
Pfam clan CL0020
InterPro IPR022365
SCOP 1bpo
SUPERFAMILY 1bpo
Clathrin heavy-chain linker
PDB 1utc EBI.jpg
clathrin terminal domain complexed with tlpwdlwtt
Identifiers
Symbol Clathrin-link
Pfam PF09268
Pfam clan CL0020
InterPro IPR015348
SCOP 1utc
SUPERFAMILY 1utc

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.

Structure[edit]

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.

In a cell, a triskelion floating in the cytoplasm binds to an adaptor protein, 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 smallest clathrin cage commonly imaged, 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.

Function[edit]

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]

See also[edit]

References[edit]

  1. ^ 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): 1255–9. doi:10.1073/pnas.73.4.1255. PMC 430241. PMID 1063406. 
  2. ^ McMahon HT. "Clathrin and its interactions with AP180.". MRC Laboratory of Molecular Biology. Retrieved 2009-04-17. "micrographs of clathrin assembly" 
  3. ^ 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): 1051–5. doi:10.1126/science.291.5506.1051. PMID 11161218. 
  4. ^ Higgins MK, McMahon HT (May 2002). "Snap-shots of clathrin-mediated endocytosis". Trends in Biochemical Sciences 27 (5): 257–63. doi:10.1016/S0968-0004(02)02089-3. PMID 12076538. 
  5. ^ Royle SJ, Bright NA, Lagnado L (April 2005). "Clathrin is required for the function of the mitotic spindle". Nature 434 (7037): 1152–1157. doi:10.1038/nature03502. PMID 15858577. 
  6. ^ 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

Further reading[edit]

External links[edit]

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

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 propeller repeat Provide feedback

Clathrin is the scaffold protein of the basket-like coat that surrounds coated vesicles. The soluble assembly unit, a triskelion, contains three heavy chains and three light chains in an extended three-legged structure. Each leg contains one heavy and one light chain. The N-terminus of the heavy chain is known as the globular domain, and is composed of seven repeats which form a beta propeller [1].

Literature references

  1. ter Haar E, Musacchio A, Harrison SC, Kirchhausen T; , Cell. 1998;95:563-573.: Atomic structure of clathrin: a beta propeller terminal domain joins an alpha zigzag linker. PUBMED:9827808 EPMC:9827808


External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR022365

This entry represents the propeller repeat found in clathrin heavy chains. The N terminus of the heavy chain is known as the globular domain, and is composed of seven repeats which form a beta propeller [PUBMED:9827808].

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].

More information about these proteins can be found at Protein of the Month: Clathrin [PUBMED:].

Domain organisation

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Alignments

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(71)
Full
(581)
Representative proteomes NCBI
(507)
Meta
(4)
RP15
(90)
RP35
(164)
RP55
(246)
RP75
(344)
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  Seed
(71)
Full
(581)
Representative proteomes NCBI
(507)
Meta
(4)
RP15
(90)
RP35
(164)
RP55
(246)
RP75
(344)
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  Seed
(71)
Full
(581)
Representative proteomes NCBI
(507)
Meta
(4)
RP15
(90)
RP35
(164)
RP55
(246)
RP75
(344)
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You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

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Curation and family details

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Seed source: [1]
Previous IDs: none
Type: Repeat
Author: Bateman A
Number in seed: 71
Number in full: 581
Average length of the domain: 38.40 aa
Average identity of full alignment: 30 %
Average coverage of the sequence by the domain: 4.84 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 21.3 21.3
Trusted cut-off 21.9 21.3
Noise cut-off 20.9 21.2
Model length: 37
Family (HMM) version: 15
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Species distribution

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Interactions

There are 2 interactions for this family. More...

Clathrin_propel Clathrin-link

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_propel domain has been found. There are 39 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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