3L4F

Crystal Structure of betaPIX Coiled-Coil Domain and Shank PDZ Complex

Summary for 3L4F

• Entry DOI: 10.2210/pdb3l4f/pdb
• Descriptor: Rho guanine nucleotide exchange factor 7, SH3 and multiple ankyrin repeat domains protein 1 (3 entities in total)
• Functional Keywords: coiled-coil, pdz, guanine-nucleotide releasing factor, phosphoprotein, sh3 domain, ank repeat, cell junction, cell membrane, membrane, postsynaptic cell membrane, synapse, signaling protein-protein binding complex, signaling protein/protein binding
• Biological source: Rattus norvegicus (rat); More
• Total number of polymer chains: 4
• Total formula weight: 36618.92

Authors

Im, Y.J.,Kang, G.B.,Lee, J.H.,Song, H.E.,Park, K.R.,Kim, E.,Song, W.K.,Park, D.,Eom, S.H. (deposition date: 2009-12-19, release date: 2010-02-16, Last modification date: 2023-11-01)

Primary citation

Im, Y.J.,Kang, G.B.,Lee, J.H.,Park, K.R.,Song, H.E.,Kim, E.,Song, W.K.,Park, D.,Eom, S.H.
Structural basis for asymmetric association of the betaPIX coiled coil and shank PDZ
J.Mol.Biol., 397:457-466, 2010

PubMed 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-sheet interaction extending to position -6 of betaPIX. The betaB-betaC loop of Shank PDZ undergoes a conformational change upon ligand binding to form the beta-sheet interaction and to accommodate the bulky side chain of Trp -5. This structural study provides a clear picture of the molecular recognition of the PDZ ligand and the asymmetric association of betaPIX CC and Shank PDZ.

PubMed: 20117114
DOI: 10.1016/j.jmb.2010.01.048

Experimental method

X-RAY DIFFRACTION (2.8 Å)