Crystal structure of a 12 ANK repeat stack from human ankyrinR

Peter Michaely, Diana R. Tomchick, Mischa Machius, Richard G W Anderson

Research output: Contribution to journalArticle

150 Citations (Scopus)

Abstract

Ankyrins are multifunctional adaptors that link specific proteins to the membrane-associated, spectrinactin cytoskeleton. The N-terminal, 'membrane-binding' domain of ankyrins contains 24 ANK repeats and mediates most binding activities. Repeats 13-24 are especially active, with known sites of interaction for the Na/K ATPase, Cl/HCO3 anion exchanger, voltagegated sodium channel, clathrin heavy chain and L1 family cell adhesion molecules. Here we report the crystal structure of a human ankyrinR construct containing ANK repeats 13-24 and a portion of the spectrin-binding domain. The ANK repeats are observed to form a contiguous spiral stack with which the spectrin-binding domain fragment associates as an extended strand. The structural information has been used to construct models of all 24 repeats of the membrane-binding domain as well as the interactions of the repeats with the Cl/HCO3 anion exchanger and clathrin. These models, together with available binding studies, suggest that ion transporters such as the anion exchanger associate in a large central cavity formed by the ANK repeat spiral, while clathrin and cell adhesion molecules associate with specific regions outside this cavity.

Original languageEnglish (US)
Pages (from-to)6387-6396
Number of pages10
JournalEMBO Journal
Volume21
Issue number23
DOIs
StatePublished - Dec 2 2002

Fingerprint

Ankyrin Repeat
Crystal structure
Chloride-Bicarbonate Antiporters
Ankyrins
Anions
Spectrin
Clathrin
Cell Adhesion Molecules
Membranes
Clathrin Heavy Chains
Neural Cell Adhesion Molecule L1
Sodium Channels
Cytoskeleton
Ions
Proteins

Keywords

  • Anion exchanger
  • ANK
  • Ankyrin
  • Clathrin
  • Spectrin

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Cite this

Crystal structure of a 12 ANK repeat stack from human ankyrinR. / Michaely, Peter; Tomchick, Diana R.; Machius, Mischa; Anderson, Richard G W.

In: EMBO Journal, Vol. 21, No. 23, 02.12.2002, p. 6387-6396.

Research output: Contribution to journalArticle

Michaely, Peter ; Tomchick, Diana R. ; Machius, Mischa ; Anderson, Richard G W. / Crystal structure of a 12 ANK repeat stack from human ankyrinR. In: EMBO Journal. 2002 ; Vol. 21, No. 23. pp. 6387-6396.
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