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Publication Abstract from PubMed

PDZ domains are protein-protein recognition modules that interact with other proteins through short sequences at the carboxyl terminus. These domains are structurally characterized by a conserved fold composed of six beta-strands and two alpha-helices. The third PDZ domain of the neuronal postsynaptic density protein 95 has an additional alpha-helix (alpha3), the role of which is not well known. In previous structures, a succinimide was identified in the beta2-beta3 loop instead of Asp332. The presence of this modified residue results in conformational changes in alpha3. In this work, crystallographic structures of the following have been solved: a truncated form of the third PDZ domain of the neuronal postsynaptic density protein 95 from which alpha3 has been removed, D332P and D332G variants of the protein, and a new crystal form of this domain showing the binding of Asp332 to the carboxylate-binding site of a symmetry-related molecule. Crystals of the wild type and variants were obtained in different space groups, which reflects the conformational plasticity of the domain. Indeed, the overall analysis of these structures suggests that the conformation of the beta2-beta3 loop is correlated with the fold acquired by alpha3. The alternate conformation of the beta2-beta3 loop affects the electrostatics of the carboxylate-binding site and might modulate the binding of different PDZ-binding motifs.

Conformational changes in the third PDZ domain of the neuronal postsynaptic density protein 95.,Camara-Artigas A, Murciano-Calles J, Martinez JC Acta Crystallogr D Struct Biol. 2019 Apr 1;75(Pt 4):381-391. doi:, 10.1107/S2059798319001980. Epub 2019 Mar 28. PMID:30988255^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.