Crystal structure of the clathrin adaptor protein 1 core

Ekaterina E. Heldwein, Eric Macia, Jing Wang, Helen L. Yin, Tomas Kirchhausen, Stephen C. Harrison

Research output: Contribution to journalArticle

133 Citations (Scopus)

Abstract

The heterotetrameric adaptor proteins (AP complexes) link the outer lattice of clathrin-coated vesicles with membrane-anchored cargo molecules. We report the crystal structure of the core of the AP-1 complex, which functions in the trans-Golgi network (TGN). Packing of complexes in the crystal generates an exceptionally long (1,135-Å) unit-cell axis, but the 6-fold noncrystallographic redundancy yields an excellent map at 4-Å resolution. The AP-1 core comprises N-terminal fragments of the two large chains, β1 and γ, and the intact medium and small chains, μ1 and σ1. Its molecular architecture closely resembles that of the core of AP-2, the plasma-membrane-specific adaptor, for which a structure has been determined. Both structures represent an "inactive" conformation with respect to binding of cargo with a tyrosine-based sorting signal. TGN localization of AP-1 depends on the small GTPase, Arf1, and the phosphoinositide, PI-4-P. We show that directed mutations of residues at a particular corner of the γ chain prevent recruitment to the TGN in cells and diminish PI-4-P-dependent, but not Arf1-dependent, liposome binding in vitro.

Original languageEnglish (US)
Pages (from-to)14108-14113
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume101
Issue number39
DOIs
StatePublished - Sep 28 2004

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Vesicular Transport Adaptor Proteins
trans-Golgi Network
Transcription Factor AP-1
Clathrin-Coated Vesicles
Proteins
Monomeric GTP-Binding Proteins
Phosphatidylinositols
Liposomes
Tyrosine
Cell Membrane
Mutation
Membranes

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Crystal structure of the clathrin adaptor protein 1 core. / Heldwein, Ekaterina E.; Macia, Eric; Wang, Jing; Yin, Helen L.; Kirchhausen, Tomas; Harrison, Stephen C.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 101, No. 39, 28.09.2004, p. 14108-14113.

Research output: Contribution to journalArticle

Heldwein, Ekaterina E. ; Macia, Eric ; Wang, Jing ; Yin, Helen L. ; Kirchhausen, Tomas ; Harrison, Stephen C. / Crystal structure of the clathrin adaptor protein 1 core. In: Proceedings of the National Academy of Sciences of the United States of America. 2004 ; Vol. 101, No. 39. pp. 14108-14113.
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