Structural basis for asymmetric association of the betaPIX coiled coil and shank PDZ

Journal of Molecular Biology
Young Jun ImSoo Hyun Eom

Abstract

betaPIX (p21-activated kinase interacting exchange factor) and Shank/ProSAP protein form a complex acting as a protein scaffold that integrates signaling pathways and regulates postsynaptic structure. Complex formation is mediated by the C-terminal PDZ binding motif of betaPIX and the Shank PDZ domain. The coiled-coil (CC) domain upstream of the PDZ binding motif allows multimerization of betaPIX, which is important for its physiological functions. We have solved the crystal structure of the betaPIX CC-Shank PDZ complex and determined the stoichiometry of complex formation. The betaPIX CC forms a 76-A-long parallel CC trimer. Despite the fact that the betaPIX CC exposes three PDZ binding motifs in the C-termini, the betaPIX trimer associates with a single Shank PDZ. One of the C-terminal ends of the CC forms an extensive beta-sheet interaction with the Shank PDZ, while the other two ends are not involved in ligand binding and form random coils. The two C-terminal ends of betaPIX have significantly lower affinity than the first PDZ binding motif due to the steric hindrance in the C-terminal tails, which results in binding of a single PDZ domain to the betaPIX trimer. The structure shows canonical class I PDZ binding with a beta-...Continue Reading

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Citations

May 23, 2015·International Journal of Molecular Sciences·Fahad BenthaniLaurent Pangon
May 8, 2010·Journal of Molecular Biology·Peter D MaceCatherine L Day
May 18, 2016·Proceedings of the National Academy of Sciences of the United States of America·Menglong ZengMingjie Zhang
Feb 24, 2018·Journal of Neurochemistry·Srinivas Kumar PonnaPetri Kursula
Aug 18, 2010·Chembiochem : a European Journal of Chemical Biology·Wendy S Iskenderian-Epps, Barbara Imperiali
Jan 11, 2019·International Journal of Molecular Sciences·Lianhua PiaoShan Chang
Apr 22, 2020·Advanced Therapeutics·Nikolaj R ChristensenKristian Strømgaard
Aug 26, 2014·Biochemical and Biophysical Research Communications·Junsen TongYoung Jun Im
Jul 9, 2021·Current Research in Structural Biology·Muhammad AliYlva Ivarsson

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