Sandbox8999: Difference between revisions
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An individual clathrin molecule is composed of three heavy chains, which each have a light chain attached to them. This structure is often referred to as a triskelion shape.<ref name="harrison" /> The heavy chains of clathrin are made of an amino-terminal, a beta-propellor domain which contain multiple repeats of the WD40 binding motif, alpha-helical zig-zags close to 30 amino acids in length, a lengthened alpha-helix where the threefold contacts, and a carboxy-terminal.<ref name="harrison" /> The aforementioned zig-zags are what create the “leg” looking structure of the triskelion.<ref name="harrison" /> A segment of the heavy chain is designed with the purpose of attaching to the light chain.<ref name="harrison" /> The heavy chain and light chain bind through one long alpha helix towards the center of the protein.<ref name="harrison" /> | An individual clathrin molecule is composed of three heavy chains, which each have a light chain attached to them. This structure is often referred to as a triskelion shape.<ref name="harrison" /> The heavy chains of clathrin are made of an amino-terminal, a beta-propellor domain which contain multiple repeats of the WD40 binding motif, alpha-helical zig-zags close to 30 amino acids in length, a lengthened alpha-helix where the threefold contacts, and a carboxy-terminal.<ref name="harrison" /> The aforementioned zig-zags are what create the “leg” looking structure of the triskelion.<ref name="harrison" /> A segment of the heavy chain is designed with the purpose of attaching to the light chain.<ref name="harrison" /> The heavy chain and light chain bind through one long alpha helix towards the center of the protein.<ref name="harrison" /> | ||
[[Image:LatticeStructure.png |frame| a) Clathrin monomer with labeled heavy and light chains b) Clathrin monomers forming a basic lattice structure.<ref name="pearse">PMID: 1063406</ref> Clathrin is made of individual triskelion components that come together to form the cage-like structure of clathrin.<ref name="crowther" /> Each vertex is composed of a triskelion leg.<ref name="crowther" /> Although there are various packing models for clathrin cage assembly, the overall theme is multiple triskelions coming together to form the cage like structure.<ref name="crowther" />]] | [[Image:LatticeStructure.png |frame| Figure 1. a) Clathrin monomer with labeled heavy and light chains b) Clathrin monomers forming a basic lattice structure.<ref name="pearse">PMID: 1063406</ref> Clathrin is made of individual triskelion components that come together to form the cage-like structure of clathrin.<ref name="crowther" /> Each vertex is composed of a triskelion leg.<ref name="crowther" /> Although there are various packing models for clathrin cage assembly, the overall theme is multiple triskelions coming together to form the cage like structure.<ref name="crowther" />]] | ||
===Lattice=== | ===Lattice=== | ||
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Individual clathrin molecules can assemble into cage-like structures. When individual clathrin molecules come together, a lattice is formed where each lattice point is associated with the center of a triskelion (from the Greek word meaning “a three legged structure”).<ref name="harrison" /> According to Crowther, R.A., clathrin vesicles are constructed from twelve pentagonal units plus a number of hexagonal units, with the number of hexagons increasing for larger clathrin coats.<ref name="crowther">PMID: 7328122 </ref> The term “cage” can be used to refer to empty shells composed only of clathrin while the term “coat” refers to clathrin in addition to associated proteins and vesicles.<ref name="crowther" /> Clathrin lattices are formed under optimal conditions of physiological pH (6.0-6.5) and in the presence of Calcium or Magnesium ions.<ref name="crowther" /> Various packing models have been investigated as to how the individual triskelion legs assemble into clathrin cages.<ref name="crowther" /> As mentioned above, the center of the triskelion legs occurs at each vertex of the cage, meaning pentagons, heptagons, and hexagons can be formed.<ref name="crowther" /> In the individual triskelion legs, the bend in the leg is 160 Angstroms from the vertex, giving rise to two models of packing: simple side-by-side packing or a cross-over type of packing,<ref name="crowther" /> Cross-over packing occurs when a hexamer of triskelions is formed with crossing over of the leg portions of the triskelions.<ref name="crowther" /> Rather than involving crossing over, simple packing refers to side by side packing of the leg portions of the triskelions.<ref name="crowther" /> | Individual clathrin molecules can assemble into cage-like structures. When individual clathrin molecules come together, a lattice is formed where each lattice point is associated with the center of a triskelion (from the Greek word meaning “a three legged structure”).<ref name="harrison" /> According to Crowther, R.A., clathrin vesicles are constructed from twelve pentagonal units plus a number of hexagonal units, with the number of hexagons increasing for larger clathrin coats.<ref name="crowther">PMID: 7328122 </ref> The term “cage” can be used to refer to empty shells composed only of clathrin while the term “coat” refers to clathrin in addition to associated proteins and vesicles.<ref name="crowther" /> Clathrin lattices are formed under optimal conditions of physiological pH (6.0-6.5) and in the presence of Calcium or Magnesium ions.<ref name="crowther" /> Various packing models have been investigated as to how the individual triskelion legs assemble into clathrin cages.<ref name="crowther" /> As mentioned above, the center of the triskelion legs occurs at each vertex of the cage, meaning pentagons, heptagons, and hexagons can be formed.<ref name="crowther" /> In the individual triskelion legs, the bend in the leg is 160 Angstroms from the vertex, giving rise to two models of packing: simple side-by-side packing or a cross-over type of packing,<ref name="crowther" /> Cross-over packing occurs when a hexamer of triskelions is formed with crossing over of the leg portions of the triskelions.<ref name="crowther" /> Rather than involving crossing over, simple packing refers to side by side packing of the leg portions of the triskelions.<ref name="crowther" /> | ||
[[Image:LaatticeStructure2.png |frame| Models of the various packing models of triskelion components of clathrin.<ref name="crowther" /> Each vertex of the polygon is made of a triskelion and the legs of the triskelion run along the edges. (a) Simple side-by-side packing model of the legs in which there is no overlap and a hexamer is formed. (b) Model of cross-over packing of the triskelion legs forming a hexamer and (c) Similar model as (b) except a pentamer is formed by the triskelions with crossing over of the leg portions.<ref name="crowther" />]] | [[Image:LaatticeStructure2.png |frame| Figure 2. Models of the various packing models of triskelion components of clathrin.<ref name="crowther" /> Each vertex of the polygon is made of a triskelion and the legs of the triskelion run along the edges. (a) Simple side-by-side packing model of the legs in which there is no overlap and a hexamer is formed. (b) Model of cross-over packing of the triskelion legs forming a hexamer and (c) Similar model as (b) except a pentamer is formed by the triskelions with crossing over of the leg portions.<ref name="crowther" />]] | ||
== Function == | == Function == | ||
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Classical endocytosis involving clathrin-coated pits and clathrin-coated vesicles is referred to as the canonical clathrin pathway.<ref name="harrison" /> Canonical clathrin-dependent pathways involve the uptake of transferrin (Tf) by transferrin receptor (TfR) and the uptake of LDL by LDL receptors (LDLR).<ref name="harrison" /> Early studies showed that LDL epidermal growth factor (Tf) bound to their specific receptors could be endocytosed within the same vesicle.<ref name="harrison" /> The receptors for these molecules are composed of tails on their cytoplasmic side that contain sequences, which determine cargo sorting and also signal for clathrin to bind.<ref name="harrison" /> Clathrin then coats these vesicles and endocytosis occurs.<ref name="harrison" /> Other pathways, such as reuptake of neurotransmitters into the synaptic cleft, are seen to have similar mechanisms to canonical clathrin pathways.<ref name="harrison" /> | Classical endocytosis involving clathrin-coated pits and clathrin-coated vesicles is referred to as the canonical clathrin pathway.<ref name="harrison" /> Canonical clathrin-dependent pathways involve the uptake of transferrin (Tf) by transferrin receptor (TfR) and the uptake of LDL by LDL receptors (LDLR).<ref name="harrison" /> Early studies showed that LDL epidermal growth factor (Tf) bound to their specific receptors could be endocytosed within the same vesicle.<ref name="harrison" /> The receptors for these molecules are composed of tails on their cytoplasmic side that contain sequences, which determine cargo sorting and also signal for clathrin to bind.<ref name="harrison" /> Clathrin then coats these vesicles and endocytosis occurs.<ref name="harrison" /> Other pathways, such as reuptake of neurotransmitters into the synaptic cleft, are seen to have similar mechanisms to canonical clathrin pathways.<ref name="harrison" /> | ||
[[Image:Endocytosis.gif |frame| Formation and dissociation of a canonical, endocytitic clathrin-coated pit.<ref name="harrison" />]] | [[Image:Endocytosis.gif |frame| Figure 3. Formation and dissociation of a canonical, endocytitic clathrin-coated pit.<ref name="harrison" />]] | ||
