The spectrin repeat: a structural platform for cytoskeletal protein assemblies.
Spectrin repeats are three-helix bundle structures which occur in a large number of diverse proteins, either as single copies or in tandem arrangements of multiple repeats. They can serve structural purposes, by coordination of cytoskeletal interactions with high spatial precision, as well as a 'switchboard' for interactions with multiple proteins with a more regulatory role. We describe the structure of the alpha-actinin spectrin repeats as a prototypical example, their assembly in a defined antiparallel dimer, and the interactions of spectrin repeats with multiple other proteins. The alpha-actinin rod domain shares several features common to other spectrin repeats. (1) The rod domain forms a rigid connection between two actin-binding domains positioned at the two ends of the alpha-actinin dimer. The exact distance and rigidity are important, for example, for organizing the muscle Z-line and maintaining its architecture during muscle contraction. (2) The spectrin repeats of alpha-actinin have evolved to make tight antiparallel homodimer contacts. (3) The spectrin repeats are important interaction sites for multiple structural and signalling proteins. The interactions of spectrin repeats are, however, diverse and defy any simple classification of their preferred interaction sites, which is possible for other domains (e.g. src-homology domains 3 or 2). Nevertheless, the binding properties of the repeats perform important roles in the biology of the proteins where they are found, and lead to the assembly of complex, multiprotein structures involved both in cytoskeletal architecture as well as in forming large signal transduction complexes.
Djinovic-Carugo
Kristina
K
Structural Biology Laboratory, Sincrotrone Trieste in Area Science Park, S.S. 14 Km 163,5, 34012 Trieste, Italy. djinovic@elettra.trieste.it
Gautel
Mathias
M
Ylänne
Jari
J
Young
Paul
P
D000185:Actinin / Q000737:chemistry / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D003598:Cytoskeletal Proteins / Q000235:genetics*; D017433:Protein Structure, Secondary; D021122:Protein Subunits; D020449:Repetitive Sequences, Amino Acid; D013049:Spectrin / Q000737:chemistry* / Q000378:metabolism
D003598:Cytoskeletal Proteins; D021122:Protein Subunits; D000185:Actinin; D013049:Spectrin