Z-band Alternately Spliced PDZ-containing protein (ZASP) is a sarcomeric Z- disk protein expressed in human cardiac and skeletal muscle that is involved in a dominant familial dilated cardiomyopathy. ZASP interacts with the last 150 amino acids of alpha-actinin-2, the major component of the Z-disk, via an N-terminal PDZ domain. ZASP and alpha-actinin-2 are thought to play an important structural role, probably by forming a ternary complex with titin Z-repeats. We have determined the structure of ZASP PDZ and characterised its interaction with alpha-actinin-2. We show that ZASP PDZ is a classical class 1 PDZ domain that recognises with micromolar affinity the carboxy- terminal sequence of an alpha-actinin-2 calmodulin-like domain. We also characterised the ternary complex ZASP/alpha-actinin-2/titin and the role of each component, showing that the alpha-actinin-2/ZASP PDZ interaction involves a binding surface distinct from that involved in the recognition of the titin Z repeats. Finally, we used the ZASP PDZ structure to model other members of the enigma family by homology and to predict their abilities to bind alpha-actinin-2.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:411600 |
| Date | January 2004 |
| Creators | Au, Yunghan |
| Publisher | University College London (University of London) |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://discovery.ucl.ac.uk/1446765/ |
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