Article
- The EMBO Journal (2002) 21, 6387 - 6396
- doi:10.1093/emboj/cdf651
Subject Categories:
Crystal structure of a 12 ANK repeat stack from human ankyrinR
Peter Michaely1, Diana R. Tomchick2, Mischa Machius2 and Richard G.W. Anderson1
- Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX 75235-9039, USA
- Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75235-9039, USA
Correspondence to:
Peter Michaely, E-mail: peter.michaely@utsouthwestern.edu
Received 25 July 2002; Accepted 17 October 2002; Revised 14 October 2002
Abstract
Ankyrins are multifunctional adaptors that link specific proteins to the membrane-associated, spectrin–actin 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, voltage-gated 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.
Keywords:
- anion exchanger,
- ANK,
- ankyrin,
- clathrin,
- spectrin



