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Life of a clathrin coat: insights from clathrin and AP structures

Nature Reviews Molecular Cell Biology volume 7, pages 32–44 (2006)Cite this article

Key Points

  • Membrane sorting between secretory and endocytic organelles is predominantly controlled by small carrier vesicles or tubules that have specific protein coats on their cytoplasmic surfaces. The most widely studied of the various membrane-transport intermediates are clathrin-coated vesicles.

  • By positioning crystal structures of domains of clathrin and auxilin (auxilin links clathrin to the 'unfoldase' Hsc70) in cryo-electron-microscopy maps of clathrin cages that were assembled in the presence of auxilin, molecular explanations have been obtained for how clathrin-coat disassembly might proceed.

  • Many clathrin adaptors, which are defined as proteins that link polymerized clathrin to membranes and their embedded proteins, have different sequences and structures, but have a common architecture that consists of folded domains that are linked by extended, structureless linkers.

  • Structural and biochemical studies on the heterotetrameric adaptor protein complexes (APs), which are the most abundant of all the clathrin adaptors, show how they carry out their numerous and often phosphorylation-regulated functions. These functions include binding protein cargo, phospholipids and clathrin, and coordinating the recruitment of many of the other proteins that are involved in assembling and subsequently disassembling clathrin-coated vesicles.

Abstract

Membrane sorting between secretory and endocytic organelles is predominantly controlled by small carrier vesicles or tubules that have specific protein coats on their cytoplasmic surfaces. Clathrin–clathrin-adaptor coats function in many steps of intracellular transport and are the most extensively studied of all transport-vesicle coats. In recent years, the determination of structures of clathrin assemblies by electron microscopy, of domains of clathrin and of its adaptors has improved our understanding of the molecular mechanisms of clathrin-coated-vesicle assembly and disassembly.

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Figure 1: Clathrin-cage reconstructions.
Figure 2: The architecture of clathrin.
Figure 3: Molecular details of clathrin interactions.
Figure 4: AP1 and AP2 at high resolution.
Figure 5: AP complexes: binding sites in the appendages and the motifs bound.

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Authors and Affiliations

  1. Department of Clinical Biochemistry, Cambridge Institute for Medical Research, University of Cambridge, Hills Road, Cambridge, CB2 2XY, UK

    Melissa A. Edeling & David Owen

  2. Department of Biological Sciences, University of Warwick, Coventry, CV4 7AL, UK

    Corinne Smith

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DATABASES

InterPro

clathrin light chain

TDs

Protein Data Bank

1B9K

1BXX

1E42

1GW5

1GYU

1IFQ

1J2J

1KY7

1KYF

1NRJ

1OM9

1W63

1W80

1XI4

FURTHER INFORMATION

David Owen's laboratory

Corinne Smith's laboratory

Glossary

ARH and Dab2

Autosomal recessive hypercholesterolaemia protein (ARH) and Disabled-2 (Dab2) are clathrin adaptors that bind to members of the low density lipoprotein (LDL)-receptor family.

α-helical hairpin

A structural motif that comprises a short α-helix joined to another α-helix by a loop. The helices lie side by side, and the motif can be repeated many times with the hairpins stacking on top of one another to form a twisting helical solenoid.

J domain

A conserved domain that stimulates ATP hydrolysis by chaperones of the 70-kDa heat-shock protein (Hsp70) family. It was first identified in the Escherichia coli co-chaperone DnaJ, but it is also found in DnaJ homologues in eukaryotes, as well as in several co-chaperones that recruit Hsp70 proteins for specific cellular processes.

AP180

(adaptor protein of 180 kDa). AP180 is another clathrin adaptor that is found in clathrin coats, but is not related to the APs (adaptor protein complexes). It is a single-chain clathrin adaptor that is composed of an ∼30-kDa helical ANTH (AP180 N-terminal homology) domain at its N terminus followed by a large unstructured region.

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Edeling, M., Smith, C. & Owen, D. Life of a clathrin coat: insights from clathrin and AP structures. Nat Rev Mol Cell Biol 7, 32–44 (2006). https://doi.org/10.1038/nrm1786

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