The Structure and Function of the Beta 2-adaptin Appendage Domain

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 2000 Aug 16

PMID 10944104

Citations 95

Authors

D J Owen

Y Vallis

B M Pearse

H T McMahon

P R Evans

Affiliations

Soon will be listed here.

Abstract

The heterotetrameric AP2 adaptor (alpha, beta 2, mu 2 and sigma 2 subunits) plays a central role in clathrin-mediated endocytosis. We present the protein recruitment function and 1.7 A resolution structure of its beta 2-appendage domain to complement those previously determined for the mu 2 subunit and alpha appendage. Using structure-directed mutagenesis, we demonstrate the ability of the beta 2 appendage alone to bind directly to clathrin and the accessory proteins AP180, epsin and eps15 at the same site. Clathrin polymerization is promoted by binding of clathrin simultaneously to the beta 2-appendage site and to a second site on the adjacent beta 2 hinge. This results in the displacement of the other ligands from the beta 2 appendage. Thus clathrin binding to an AP2-accessory protein complex would cause the controlled release of accessory proteins at sites of vesicle formation.

Citing Articles

Recruitment of clathrin to intracellular membranes is sufficient for vesicle formation.

Kuey C, Sittewelle M, Larocque G, Hernandez-Gonzalez M, Royle S Elife. 2022; 11.

PMID: 35852853 PMC: 9337851. DOI: 10.7554/eLife.78929.

Clathrin Light Chains: Not to Be Taken so Lightly.

Das J, Tiwari M, Subramanyam D Front Cell Dev Biol. 2021; 9:774587.

PMID: 34970544 PMC: 8712872. DOI: 10.3389/fcell.2021.774587.

Multi-modal adaptor-clathrin contacts drive coated vesicle assembly.

Smith S, Larocque G, Wood K, Morris K, Roseman A, Sessions R EMBO J. 2021; 40(19):e108795.

PMID: 34487371 PMC: 8488560. DOI: 10.15252/embj.2021108795.

Characterization of a Novel SARS-CoV-2 Genetic Variant with Distinct Spike Protein Mutations.

Gladkikh A, Dolgova A, Dedkov V, Sbarzaglia V, Kanaeva O, Popova A Viruses. 2021; 13(6).

PMID: 34072569 PMC: 8230012. DOI: 10.3390/v13061029.

Viral Interactions with Adaptor-Protein Complexes: A Ubiquitous Trait among Viral Species.

Strazic Geljic I, Kucan Brlic P, Musak L, Karner D, Ambriovic-Ristov A, Jonjic S Int J Mol Sci. 2021; 22(10).

PMID: 34067854 PMC: 8156722. DOI: 10.3390/ijms22105274.

References

Ybe J, Brodsky F, Hofmann K, Lin K, Liu S, Chen L . Clathrin self-assembly is mediated by a tandemly repeated superhelix. Nature. 1999; 399(6734):371-5. DOI: 10.1038/20708. View

Owen D, Vallis Y, Noble M, Hunter J, Dafforn T, Evans P . A structural explanation for the binding of multiple ligands by the alpha-adaptin appendage domain. Cell. 1999; 97(6):805-15. DOI: 10.1016/s0092-8674(00)80791-6. View

Hao W, Luo Z, Zheng L, Prasad K, Lafer E . AP180 and AP-2 interact directly in a complex that cooperatively assembles clathrin. J Biol Chem. 1999; 274(32):22785-94. DOI: 10.1074/jbc.274.32.22785. View

Traub L, Downs M, Westrich J, Fremont D . Crystal structure of the alpha appendage of AP-2 reveals a recruitment platform for clathrin-coat assembly. Proc Natl Acad Sci U S A. 1999; 96(16):8907-12. PMC: 17706. DOI: 10.1073/pnas.96.16.8907. View

Gaidarov I, Keen J . Phosphoinositide-AP-2 interactions required for targeting to plasma membrane clathrin-coated pits. J Cell Biol. 1999; 146(4):755-64. PMC: 2156139. DOI: 10.1083/jcb.146.4.755. View

Gaidarov I, Santini F, Warren R, Keen J . Spatial control of coated-pit dynamics in living cells. Nat Cell Biol. 1999; 1(1):1-7. DOI: 10.1038/8971. View

Roos J, Kelly R . The endocytic machinery in nerve terminals surrounds sites of exocytosis. Curr Biol. 1999; 9(23):1411-4. DOI: 10.1016/s0960-9822(00)80087-1. View

Kirchhausen T . Adaptors for clathrin-mediated traffic. Annu Rev Cell Dev Biol. 1999; 15:705-32. DOI: 10.1146/annurev.cellbio.15.1.705. View

Mellman I, Warren G . The road taken: past and future foundations of membrane traffic. Cell. 2000; 100(1):99-112. DOI: 10.1016/s0092-8674(00)81687-6. View

10.

ter Haar E, Harrison S, Kirchhausen T . Peptide-in-groove interactions link target proteins to the beta-propeller of clathrin. Proc Natl Acad Sci U S A. 2000; 97(3):1096-100. PMC: 15533. DOI: 10.1073/pnas.97.3.1096. View

11.

Drake M, Downs M, Traub L . Epsin binds to clathrin by associating directly with the clathrin-terminal domain. Evidence for cooperative binding through two discrete sites. J Biol Chem. 2000; 275(9):6479-89. DOI: 10.1074/jbc.275.9.6479. View

12.

Pearse B, Smith C, Owen D . Clathrin coat construction in endocytosis. Curr Opin Struct Biol. 2000; 10(2):220-8. DOI: 10.1016/s0959-440x(00)00071-3. View

13.

Greene B, Liu S, Wilde A, Brodsky F . Complete reconstitution of clathrin basket formation with recombinant protein fragments: adaptor control of clathrin self-assembly. Traffic. 2001; 1(1):69-75. DOI: 10.1034/j.1600-0854.2000.010110.x. View

14.

. The CCP4 suite: programs for protein crystallography. Acta Crystallogr D Biol Crystallogr. 1994; 50(Pt 5):760-3. DOI: 10.1107/S0907444994003112. View

15.

Abrahams J, Leslie A . Methods used in the structure determination of bovine mitochondrial F1 ATPase. Acta Crystallogr D Biol Crystallogr. 1996; 52(Pt 1):30-42. DOI: 10.1107/S0907444995008754. View

16.

Murshudov G, Vagin A, Dodson E . Refinement of macromolecular structures by the maximum-likelihood method. Acta Crystallogr D Biol Crystallogr. 1997; 53(Pt 3):240-55. DOI: 10.1107/S0907444996012255. View

17.

Murphy J, Keen J . Recognition sites for clathrin-associated proteins AP-2 and AP-3 on clathrin triskelia. J Biol Chem. 1992; 267(15):10850-5. View

18.

Nicholls A, Sharp K, Honig B . Protein folding and association: insights from the interfacial and thermodynamic properties of hydrocarbons. Proteins. 1991; 11(4):281-96. DOI: 10.1002/prot.340110407. View

19.

Traub L . Clathrin-associated adaptor proteins - putting it all together. Trends Cell Biol. 1997; 7(2):43-6. DOI: 10.1016/S0962-8924(96)20042-X. View

20.

Morris S, Mann A, Ungewickell E . Analysis of 100-180-kDa phosphoproteins in clathrin-coated vesicles from bovine brain. J Biol Chem. 1990; 265(6):3354-7. View