Cavity architecture based modulation of ligand binding tunnels in plant START domains
The Steroidogenic acute regulatory protein (StAR)-related lipid transfer (START) domain represents an evolutionarily conserved superfamily of lipid transfer proteins widely distributed across the tree of life. Despite significant expansion in plants, knowledge about this domain remains inadequate in...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-01-01
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| Series: | Computational and Structural Biotechnology Journal |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2001037023002726 |
| _version_ | 1797384057689997312 |
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| author | Sanjeet Kumar Mahtha Kamlesh Kumari Vineet Gaur Gitanjali Yadav |
| author_facet | Sanjeet Kumar Mahtha Kamlesh Kumari Vineet Gaur Gitanjali Yadav |
| author_sort | Sanjeet Kumar Mahtha |
| collection | DOAJ |
| description | The Steroidogenic acute regulatory protein (StAR)-related lipid transfer (START) domain represents an evolutionarily conserved superfamily of lipid transfer proteins widely distributed across the tree of life. Despite significant expansion in plants, knowledge about this domain remains inadequate in plants. In this work, we explore the role of cavity architectural modulations in START protein evolution and functional diversity. We use deep-learning approaches to generate plant START domain models, followed by surface accessibility studies and a comprehensive structural investigation of the rice START family. We validate 28 rice START domain models, delineate binding cavities, measure pocket volumes, and compare these with mammalian counterparts to understand evolution of binding preferences. Overall, plant START domains retain the ancestral α/β helix-grip signature, but we find subtle variation in cavity architectures, resulting in significantly smaller ligand-binding tunnels in the plant kingdom. We identify cavity lining residues (CLRs) responsible for reduction in ancestral tunnel space, and these appear to be class specific, and unique to plants, providing a mechanism for the observed shift in domain function. For instance, mammalian cavity lining residues A135, G181 and A192 have evolved to larger CLRs across the plant kingdom, contributing to smaller sizes, minimal STARTs being the largest, while members of type-IV HD-Zip family show almost complete obliteration of lipid binding cavities, consistent with their present-day DNA binding functions. In summary, this work quantifies plant START structural & functional divergence, bridging current knowledge gaps. |
| first_indexed | 2024-03-08T21:29:59Z |
| format | Article |
| id | doaj.art-3f4ea3c9648246698cce113434b6330e |
| institution | Directory Open Access Journal |
| issn | 2001-0370 |
| language | English |
| last_indexed | 2024-03-08T21:29:59Z |
| publishDate | 2023-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Computational and Structural Biotechnology Journal |
| spelling | doaj.art-3f4ea3c9648246698cce113434b6330e2023-12-21T07:31:53ZengElsevierComputational and Structural Biotechnology Journal2001-03702023-01-012139463963Cavity architecture based modulation of ligand binding tunnels in plant START domainsSanjeet Kumar Mahtha0Kamlesh Kumari1Vineet Gaur2Gitanjali Yadav3National Institute of Plant Genome Research, New Delhi 110067, IndiaNational Institute of Plant Genome Research, New Delhi 110067, IndiaNational Institute of Plant Genome Research, New Delhi 110067, IndiaCorresponding author.; National Institute of Plant Genome Research, New Delhi 110067, IndiaThe Steroidogenic acute regulatory protein (StAR)-related lipid transfer (START) domain represents an evolutionarily conserved superfamily of lipid transfer proteins widely distributed across the tree of life. Despite significant expansion in plants, knowledge about this domain remains inadequate in plants. In this work, we explore the role of cavity architectural modulations in START protein evolution and functional diversity. We use deep-learning approaches to generate plant START domain models, followed by surface accessibility studies and a comprehensive structural investigation of the rice START family. We validate 28 rice START domain models, delineate binding cavities, measure pocket volumes, and compare these with mammalian counterparts to understand evolution of binding preferences. Overall, plant START domains retain the ancestral α/β helix-grip signature, but we find subtle variation in cavity architectures, resulting in significantly smaller ligand-binding tunnels in the plant kingdom. We identify cavity lining residues (CLRs) responsible for reduction in ancestral tunnel space, and these appear to be class specific, and unique to plants, providing a mechanism for the observed shift in domain function. For instance, mammalian cavity lining residues A135, G181 and A192 have evolved to larger CLRs across the plant kingdom, contributing to smaller sizes, minimal STARTs being the largest, while members of type-IV HD-Zip family show almost complete obliteration of lipid binding cavities, consistent with their present-day DNA binding functions. In summary, this work quantifies plant START structural & functional divergence, bridging current knowledge gaps.http://www.sciencedirect.com/science/article/pii/S2001037023002726START DomainsOryza sativaLipid binding tunnelsBinding pocketsFold predictionDeep learning |
| spellingShingle | Sanjeet Kumar Mahtha Kamlesh Kumari Vineet Gaur Gitanjali Yadav Cavity architecture based modulation of ligand binding tunnels in plant START domains Computational and Structural Biotechnology Journal START Domains Oryza sativa Lipid binding tunnels Binding pockets Fold prediction Deep learning |
| title | Cavity architecture based modulation of ligand binding tunnels in plant START domains |
| title_full | Cavity architecture based modulation of ligand binding tunnels in plant START domains |
| title_fullStr | Cavity architecture based modulation of ligand binding tunnels in plant START domains |
| title_full_unstemmed | Cavity architecture based modulation of ligand binding tunnels in plant START domains |
| title_short | Cavity architecture based modulation of ligand binding tunnels in plant START domains |
| title_sort | cavity architecture based modulation of ligand binding tunnels in plant start domains |
| topic | START Domains Oryza sativa Lipid binding tunnels Binding pockets Fold prediction Deep learning |
| url | http://www.sciencedirect.com/science/article/pii/S2001037023002726 |
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