Solution structure of ZASP PDZ domain: Implications for sarcomere ultrastructure and enigma family redundancy

Yunghan Au, R. Andrew Atkinson, Remo Guerrini, Geoff Kelly, Catherine Joseph, Steven R. Martin, Frederick W. Muskett, Alberto Pallavicini, Georgine Faulkner, Annalisa Pastore

Research output: Contribution to journalArticlepeer-review

44 Scopus citations

Abstract

Z band alternately spliced PDZ-containing protein (ZASP) is a sarcomere Z disk protein expressed in human cardiac and skeletal muscle that is thought to be involved in a dominant familial dilated cardiomyopathy. The N-terminal PDZ domain of ZASP interacts with the C terminus of α-actinin-2, the major component of the Z disk, probably by forming a ternary complex with titin Z repeats. We have determined the structure of ZASP PDZ by NMR and showed that it is a classical class 1 PDZ domain that recognizes the carboxy-terminal sequence of an α-actinin-2 calmodulin-like domain with micromolar affinity. We also characterized the role of each component in the ternary complex ZASP/α-actinin-2/titin, showing that the α-actinin-2/ZASP PDZ interaction involves a binding surface distinct from that recognized by the titin Z repeats. ZASP PDZ structure was used to model other members of the enigma family by homology and to predict their abilities to bind α-actinin-2.

Original languageEnglish
Pages (from-to)611-622
Number of pages12
JournalStructure
Volume12
Issue number4
DOIs
StatePublished - Apr 2004
Externally publishedYes

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