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Requirement of N-terminal cysteines of PSD-95 for PSD-95 multimerization and ternary complex formation, but not for binding to potassium channel Kv1.4
被引:73
作者:
Hsueh, YP
Sheng, M
[1
]
机构:
[1] Howard Hughes Med Inst, Boston, MA 02114 USA
[2] Massachusetts Gen Hosp, Dept Neurobiol, Boston, MA 02114 USA
[3] Harvard Univ, Sch Med, Boston, MA 02114 USA
关键词:
D O I:
10.1074/jbc.274.1.532
中图分类号:
Q5 [生物化学];
Q7 [分子生物学];
学科分类号:
071010 ;
081704 ;
摘要:
The PSD-95 family of PSD-95/Discs large/ZO-1 (PDZ) domain-containing proteins plays a role in the clustering and localization of specific ion channels and receptors at synapses. Previous studies have shown that PSD-95 forms multimers through an N-terminal region (termed the N-segment) and that the multimerization of PSD-95 is critical for its ability to cluster Shaker-type potassium channel Kv1.4 in heterologous cells. We show here that the PSD-95 N-segment functions as a multimerization domain only when located at the N-terminal end of a heterologous protein. A pair of N-terminal cysteines, Cys(3) and Cys(5), is essential for the ability of PSD-95 to self-associate and to form cell surface clusters with Kv1.4. However, PSD-95 mutants lacking these cysteine residues retain their ability to associate with membranes and to bind to Kv1.4, Unlike wild type PSD-95, the cysteine mutant of PSD-95 cannot form a ternary complex with Kv1.4 and the cell adhesion molecule Fas-ciclin II. These results suggest that the N-terminal cysteines are essential for PSD-95 multimerization and that multimerization is required for simultaneous binding of multiple membrane protein ligands by PSD-95.
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页码:532 / 536
页数:5
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