Solution structure of ZASP PDZ domain; implications for sarcomere ultrastructure and enigma family redundancy

Structure. 2004 Apr;12(4):611-22. doi: 10.1016/j.str.2004.02.019.

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 alpha-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 alpha-actinin-2 calmodulin-like domain with micromolar affinity. We also characterized the role of each component in the ternary complex ZASP/alpha-actinin-2/titin, showing that the alpha-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 alpha-actinin-2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actinin / metabolism
  • Adaptor Proteins, Signal Transducing
  • Carrier Proteins / chemistry*
  • Carrier Proteins / metabolism
  • Connectin
  • Homeodomain Proteins / chemistry*
  • Homeodomain Proteins / metabolism
  • Humans
  • LIM Domain Proteins
  • Magnetic Resonance Spectroscopy
  • Models, Molecular
  • Muscle Proteins / metabolism
  • Protein Kinases / metabolism
  • Protein Structure, Tertiary
  • Sarcomeres / chemistry*
  • Sarcomeres / metabolism

Substances

  • ACTN2 protein, human
  • Adaptor Proteins, Signal Transducing
  • Carrier Proteins
  • Connectin
  • Homeodomain Proteins
  • LDB3 protein, human
  • LIM Domain Proteins
  • Muscle Proteins
  • TTN protein, human
  • Actinin
  • Protein Kinases

Associated data

  • PDB/1RGW