pH-Driven Polymorphic Behaviour of the Third PDZ Domain of PSD95: The Role of Electrostatic Interactions
Metadatos
Mostrar el registro completo del ítemAutor
Salinas García, Mª Carmen; Gavira Gallardo, José Antonio; Murciano Calles, Javier; Martínez Herrerías, José CristóbalEditorial
MDPI
Materia
PDZ domain X-ray structures Conformational changes Polymorphs Electrostatic interactions
Fecha
2023-01-24Referencia bibliográfica
Salinas-García, M.C... [et al.]. pH-Driven Polymorphic Behaviour of the Third PDZ Domain of PSD95: The Role of Electrostatic Interactions. Crystals 2023, 13, 218. [https://doi.org/10.3390/cryst13020218]
Patrocinador
Junta de Andalucia; European Commission UAL18-BIO-B005-B PY20_00149; Spanish Government PID2020-116261GB-I00Resumen
The PDZ domains are modular domains that recognise short linear C-terminal sequences
in proteins that organise the formation of complex multi-component assemblies. We have crystallised
the third PDZ domain of the neuronal postsynaptic density-95 protein (PSD95-PDZ3) at mildly acidic
pH conditions and obtained up to four polymorphs. Thus, below pH 4.0, the protein crystallised into
prism-shaped crystals that belonged to the trigonal space group P3112. In contrast, above this pH
value, the crystals’ shape changes to long needles belonging to the monoclinic P21 and two different
orthorhombic packings of the P212121 space group. In addition, all the polymorphs share the main
crystallographic interface, where the sidechain of the Asp332 imitates the binding of the C-terminal
moiety to the canonical binding motif. Furthermore, we have analysed how changes in the ionisation
state of some specific residues might be critical for crystallising the different polymorphs. The analysis
of these polymorphs provides clues on the relevance of specific protein-protein interactions in protein
crystallisation. However, these structures allow dissecting those electrostatic interactions that play
a role in the conformation adopted by some residues and the extra-domain components upon binding
C-terminal sequences.