Wavelet coherence phase analysis decodes the universal switching mechanism of Ras GTPase superfamily
Summary: The Ras superfamily of GTPases regulate critical cellular processes by shuttling between GTP-bound ON and GDP-bound OFF states. This switching mechanism is attributed to the conformational changes in two loops, SWI and SWII, upon GTP binding and hydrolysis. Since these conformational change...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-07-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004223011082 |
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| author | Zenia Motiwala Anand S. Sandholu Durba Sengupta Kiran Kulkarni |
| author_facet | Zenia Motiwala Anand S. Sandholu Durba Sengupta Kiran Kulkarni |
| author_sort | Zenia Motiwala |
| collection | DOAJ |
| description | Summary: The Ras superfamily of GTPases regulate critical cellular processes by shuttling between GTP-bound ON and GDP-bound OFF states. This switching mechanism is attributed to the conformational changes in two loops, SWI and SWII, upon GTP binding and hydrolysis. Since these conformational changes vary across the Ras superfamily, there is no generic parameter to define their functional states. A unique wavelet coherence (WC) analysis-based approach developed here shows that the structural changes in switch regions could be mapped onto the wavelet coherence phase couplings (WPCs). Thus, WPCs could serve as unique parameters to define their functional states. Disentanglement of WPCs in oncogenic GTPases shows how breakdown of structural allostery leads to their aberrant function. These observations stand out even for simulated ensemble of switch region conformers. Overall, for the first time, we show that WPCs could unravel the latent structural deviations in Ras proteins to decode their universal switching mechanism. |
| first_indexed | 2024-03-12T22:22:33Z |
| format | Article |
| id | doaj.art-422df69e8ea94c1194bb2aed13f9877b |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-03-12T22:22:33Z |
| publishDate | 2023-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-422df69e8ea94c1194bb2aed13f9877b2023-07-23T04:55:14ZengElsevieriScience2589-00422023-07-01267107031Wavelet coherence phase analysis decodes the universal switching mechanism of Ras GTPase superfamilyZenia Motiwala0Anand S. Sandholu1Durba Sengupta2Kiran Kulkarni3Division of Biochemical Sciences, CSIR-National Chemical Laboratory, Pune 411008, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, IndiaDivision of Biochemical Sciences, CSIR-National Chemical Laboratory, Pune 411008, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, IndiaAcademy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India; Division of Physical and Material Chemistry, CSIR-National Chemical Laboratory, Pune 411008, IndiaDivision of Biochemical Sciences, CSIR-National Chemical Laboratory, Pune 411008, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India; Corresponding authorSummary: The Ras superfamily of GTPases regulate critical cellular processes by shuttling between GTP-bound ON and GDP-bound OFF states. This switching mechanism is attributed to the conformational changes in two loops, SWI and SWII, upon GTP binding and hydrolysis. Since these conformational changes vary across the Ras superfamily, there is no generic parameter to define their functional states. A unique wavelet coherence (WC) analysis-based approach developed here shows that the structural changes in switch regions could be mapped onto the wavelet coherence phase couplings (WPCs). Thus, WPCs could serve as unique parameters to define their functional states. Disentanglement of WPCs in oncogenic GTPases shows how breakdown of structural allostery leads to their aberrant function. These observations stand out even for simulated ensemble of switch region conformers. Overall, for the first time, we show that WPCs could unravel the latent structural deviations in Ras proteins to decode their universal switching mechanism.http://www.sciencedirect.com/science/article/pii/S2589004223011082BiomoleculesStructural biologyProtein structure aspects |
| spellingShingle | Zenia Motiwala Anand S. Sandholu Durba Sengupta Kiran Kulkarni Wavelet coherence phase analysis decodes the universal switching mechanism of Ras GTPase superfamily iScience Biomolecules Structural biology Protein structure aspects |
| title | Wavelet coherence phase analysis decodes the universal switching mechanism of Ras GTPase superfamily |
| title_full | Wavelet coherence phase analysis decodes the universal switching mechanism of Ras GTPase superfamily |
| title_fullStr | Wavelet coherence phase analysis decodes the universal switching mechanism of Ras GTPase superfamily |
| title_full_unstemmed | Wavelet coherence phase analysis decodes the universal switching mechanism of Ras GTPase superfamily |
| title_short | Wavelet coherence phase analysis decodes the universal switching mechanism of Ras GTPase superfamily |
| title_sort | wavelet coherence phase analysis decodes the universal switching mechanism of ras gtpase superfamily |
| topic | Biomolecules Structural biology Protein structure aspects |
| url | http://www.sciencedirect.com/science/article/pii/S2589004223011082 |
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