Sandbox8999: Difference between revisions

{{STRUCTURE_3lvg|  PDB=3lvg  | SIZE=400| SCENE= |right|CAPTION=Bovine clathrin heavy (grey, green, pink) and light (yellow, magenta, cyan) chains, [[3lvg]] }}'''Clathrin''' originates from the Latin word clāthrāre, meaning “to provide with a lattice”. Clathrin is a protein involved in receptor-mediated endocytosis. <ref name="harrison"> Harrison, S. C., Kirchhausen, T., & Owen, D. (2014). Molecular structure, function, and dynamics of clathrin-mediated membrane traffic. ''Cold Spring Harbor Perspectives in Biology.'' [http://dx.doi.org/10.1101/cshperspect.a016725 doi: 10.1101/cshperspect.a016725]</ref> It was not discovered until 1975 by Barbara Pearse, a British biological scientist. Clathrin is a protein resembling a triskelion shape and is composed of three heavy chains and three light chains which come together to form a polyhedral lattice similar to a cage.<ref name="harrison" /> The three heavy chains resemble three legs protruding from a center point. Some of the major functions of clathrin include lysosomal targeting, receptor-mediated endocytosis, and organelle biogenesis from the trans-Golgi network. <ref name="wakeham">Wakeham, D. E., et al. (2003). Clathrin self-assembly involves coordinated weak interactions favorable for cellular recognition. ''The Embo Journal.'' [http://dx.doi.org/10.1093/emboj/cdg511 doi:  10.1093/emboj/cdg511]</ref> The polyhedral lattice shape of clathrin largely determines its functionality, in that there are many binding sites for proteins on the heavy chains of the lattice as well. <ref name="ungewickell">Ungewickell, E., & Brandon, D. (1981). Assembly units of clathrin coats. ''Nature, 289'', 420-42. [http://dx.doi.org/10.1038/289420a0 doi: 10.1038/289420a0]</ref>

An individual clathrin molecule is composed of three heavy chains, each being attached to a light chain. 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 containing 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" /> Part of the heavy chain is designated to bind to the light chains, of which there are two variations in mammals.   The heavy chain and light chain bind through one long alpha helix towards the center of the protein.<ref name="harrison" />

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 12 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 where “coat” refers to clathrin plus 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 are formed with crossing over of the leg portions of the triskelions<ref name="crowther" />. Simple packing does not involve crossing over, but side by side packing of the leg portions of the triskelions<ref name="crowther" />.