TY - JOUR
T1 - Solution structure of ZASP PDZ domain
T2 - Implications for sarcomere ultrastructure and enigma family redundancy
AU - Au, Yunghan
AU - Atkinson, R. Andrew
AU - Guerrini, Remo
AU - Kelly, Geoff
AU - Joseph, Catherine
AU - Martin, Steven R.
AU - Muskett, Frederick W.
AU - Pallavicini, Alberto
AU - Faulkner, Georgine
AU - Pastore, Annalisa
N1 - Funding Information:
The authors wish to thank T. Frenkiel of the MRC Biomedical NMR Centre, NIMR for technical assistance. The financial support of Telethon-Italy to G.F. (Grant 1278) is gratefully acknowledged.
PY - 2004/4
Y1 - 2004/4
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=11144358221&partnerID=8YFLogxK
U2 - 10.1016/j.str.2004.02.019
DO - 10.1016/j.str.2004.02.019
M3 - Article
C2 - 15062084
AN - SCOPUS:11144358221
SN - 0969-2126
VL - 12
SP - 611
EP - 622
JO - Structure
JF - Structure
IS - 4
ER -