Crystal structure of a 12 ANK repeat stack from human ankyrinR.
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/HCO(3) 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/HCO(3) 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.
Michaely
Peter
P
Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX 75235-9039, USA. peter.michaely@utsouthwestern.edu
Tomchick
Diana R
DR
Machius
Mischa
M
Anderson
Richard G W
RG
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D017487:Ankyrins / Q000737:chemistry*; D018360:Crystallography, X-Ray; D006801:Humans; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary
D017487:Ankyrins