pH-Driven Polymorphic Behaviour of the Third PDZ Domain of PSD95: The Role of Electrostatic Interactions
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 an...
| Main Authors: | , , , , , , , |
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| Format: | info:eu-repo/semantics/article |
| Language: | English |
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MDPI
2023
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| Subjects: | |
| Online Access: | http://hdl.handle.net/10835/14165 |
| _version_ | 1789406656400982016 |
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| author | Salinas García, María Del Carmen Plaza Garrido, Marina Gavira, Jose A. Murciano‐Calles, Javier Andújar Sánchez, Montserrat Ortiz Salmerón, Emilia Martinez, Jose C. Cámara Artigas, Ana María |
| author_facet | Salinas García, María Del Carmen Plaza Garrido, Marina Gavira, Jose A. Murciano‐Calles, Javier Andújar Sánchez, Montserrat Ortiz Salmerón, Emilia Martinez, Jose C. Cámara Artigas, Ana María |
| author_sort | Salinas García, María Del Carmen |
| collection | DSpace |
| description | 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. |
| format | info:eu-repo/semantics/article |
| id | oai:repositorio.ual.es:10835-14165 |
| institution | Universidad de Cuenca |
| language | English |
| publishDate | 2023 |
| publisher | MDPI |
| record_format | dspace |
| spelling | oai:repositorio.ual.es:10835-141652023-04-12T19:47:56Z pH-Driven Polymorphic Behaviour of the Third PDZ Domain of PSD95: The Role of Electrostatic Interactions Salinas García, María Del Carmen Plaza Garrido, Marina Gavira, Jose A. Murciano‐Calles, Javier Andújar Sánchez, Montserrat Ortiz Salmerón, Emilia Martinez, Jose C. Cámara Artigas, Ana María PDZ domain X‐ray structures conformational changes polymorphs electrostatic interactions 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. 2023-01-25T18:04:19Z 2023-01-25T18:04:19Z 2023-01-24 info:eu-repo/semantics/article 2073-4352 http://hdl.handle.net/10835/14165 10.3390/cryst13020218 en https://www.mdpi.com/2073-4352/13/2/218 Attribution-NonCommercial-NoDerivatives 4.0 Internacional http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess MDPI |
| spellingShingle | PDZ domain X‐ray structures conformational changes polymorphs electrostatic interactions Salinas García, María Del Carmen Plaza Garrido, Marina Gavira, Jose A. Murciano‐Calles, Javier Andújar Sánchez, Montserrat Ortiz Salmerón, Emilia Martinez, Jose C. Cámara Artigas, Ana María pH-Driven Polymorphic Behaviour of the Third PDZ Domain of PSD95: The Role of Electrostatic Interactions |
| title | pH-Driven Polymorphic Behaviour of the Third PDZ Domain of PSD95: The Role of Electrostatic Interactions |
| title_full | pH-Driven Polymorphic Behaviour of the Third PDZ Domain of PSD95: The Role of Electrostatic Interactions |
| title_fullStr | pH-Driven Polymorphic Behaviour of the Third PDZ Domain of PSD95: The Role of Electrostatic Interactions |
| title_full_unstemmed | pH-Driven Polymorphic Behaviour of the Third PDZ Domain of PSD95: The Role of Electrostatic Interactions |
| title_short | pH-Driven Polymorphic Behaviour of the Third PDZ Domain of PSD95: The Role of Electrostatic Interactions |
| title_sort | ph-driven polymorphic behaviour of the third pdz domain of psd95: the role of electrostatic interactions |
| topic | PDZ domain X‐ray structures conformational changes polymorphs electrostatic interactions |
| url | http://hdl.handle.net/10835/14165 |
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