Comparing Native Crystal Structures and AlphaFold2 Predicted Water-Soluble G Protein-Coupled Receptor QTY Variants
Accurate predictions of 3-dimensional protein structures by AlphaFold2 is a game-changer for biology, especially for structural biology. Here we present the studies of several native chemokine receptors including CCR5, CCR9, CXCR2 and CXCR4 determined by X-ray crystallography, and their water-solubl...
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MDPI AG
2021-11-01
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| Series: | Life |
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| Online Access: | https://www.mdpi.com/2075-1729/11/12/1285 |
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| author | Michael A. Skuhersky Fei Tao Rui Qing Eva Smorodina David Jin Shuguang Zhang |
| author_facet | Michael A. Skuhersky Fei Tao Rui Qing Eva Smorodina David Jin Shuguang Zhang |
| author_sort | Michael A. Skuhersky |
| collection | DOAJ |
| description | Accurate predictions of 3-dimensional protein structures by AlphaFold2 is a game-changer for biology, especially for structural biology. Here we present the studies of several native chemokine receptors including CCR5, CCR9, CXCR2 and CXCR4 determined by X-ray crystallography, and their water-soluble QTY counter parts predicted by AlphaFold2. In the native structures, there are hydrophobic amino acids leucine (L), isoleucine (I), valine (V) and phenylalanine (F) in the transmembrane helices. These hydrophobic amino acids are systematically replaced by hydrophilic amino acids glutamine (Q), threonine (T), and tyrosine (Y). Thus, the QTY variants become water-soluble. We also present the superimposed structures of native CCR10, CXCR5, CXCR7 and an olfactory receptor OR1D2 and their water-soluble QTY variants. Since the CryoEM structural determinations for the QTY variants of CCR10<sup>QTY</sup> and OR1D2<sup>QTY</sup> are in progress, it will be of interest to compare them when the structures become available. The superimposed structures show remarkable similarity within RMSD 1Å–2Å despite significant sequence differences (~26%–~33%). We also show the differences of hydrophobicity patches between the native GPCR and their QTY variants. Our study provides insight into the subtle differences between the hydrophobic helices and hydrophilic helices, and may further stimulate designs of water-soluble membrane proteins and other aggregated proteins. |
| first_indexed | 2024-03-10T03:43:34Z |
| format | Article |
| id | doaj.art-0d357ddd22b54adcbc8c3513112222bb |
| institution | Directory Open Access Journal |
| issn | 2075-1729 |
| language | English |
| last_indexed | 2024-03-10T03:43:34Z |
| publishDate | 2021-11-01 |
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| series | Life |
| spelling | doaj.art-0d357ddd22b54adcbc8c3513112222bb2023-11-23T09:13:15ZengMDPI AGLife2075-17292021-11-011112128510.3390/life11121285Comparing Native Crystal Structures and AlphaFold2 Predicted Water-Soluble G Protein-Coupled Receptor QTY VariantsMichael A. Skuhersky0Fei Tao1Rui Qing2Eva Smorodina3David Jin4Shuguang Zhang5Laboratory of Molecular Architecture, Media Lab E15-391, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USALaboratory of Molecular Architecture, Media Lab E15-391, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USALaboratory of Molecular Architecture, Media Lab E15-391, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USAFaculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, 119991 Moscow, RussiaAvalon GloboCare Corp., Freehold, NJ 07728, USALaboratory of Molecular Architecture, Media Lab E15-391, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USAAccurate predictions of 3-dimensional protein structures by AlphaFold2 is a game-changer for biology, especially for structural biology. Here we present the studies of several native chemokine receptors including CCR5, CCR9, CXCR2 and CXCR4 determined by X-ray crystallography, and their water-soluble QTY counter parts predicted by AlphaFold2. In the native structures, there are hydrophobic amino acids leucine (L), isoleucine (I), valine (V) and phenylalanine (F) in the transmembrane helices. These hydrophobic amino acids are systematically replaced by hydrophilic amino acids glutamine (Q), threonine (T), and tyrosine (Y). Thus, the QTY variants become water-soluble. We also present the superimposed structures of native CCR10, CXCR5, CXCR7 and an olfactory receptor OR1D2 and their water-soluble QTY variants. Since the CryoEM structural determinations for the QTY variants of CCR10<sup>QTY</sup> and OR1D2<sup>QTY</sup> are in progress, it will be of interest to compare them when the structures become available. The superimposed structures show remarkable similarity within RMSD 1Å–2Å despite significant sequence differences (~26%–~33%). We also show the differences of hydrophobicity patches between the native GPCR and their QTY variants. Our study provides insight into the subtle differences between the hydrophobic helices and hydrophilic helices, and may further stimulate designs of water-soluble membrane proteins and other aggregated proteins.https://www.mdpi.com/2075-1729/11/12/1285chemokine receptorsmembrane protein designprotein structural predictionsQTY codewater-soluble GPCRs |
| spellingShingle | Michael A. Skuhersky Fei Tao Rui Qing Eva Smorodina David Jin Shuguang Zhang Comparing Native Crystal Structures and AlphaFold2 Predicted Water-Soluble G Protein-Coupled Receptor QTY Variants Life chemokine receptors membrane protein design protein structural predictions QTY code water-soluble GPCRs |
| title | Comparing Native Crystal Structures and AlphaFold2 Predicted Water-Soluble G Protein-Coupled Receptor QTY Variants |
| title_full | Comparing Native Crystal Structures and AlphaFold2 Predicted Water-Soluble G Protein-Coupled Receptor QTY Variants |
| title_fullStr | Comparing Native Crystal Structures and AlphaFold2 Predicted Water-Soluble G Protein-Coupled Receptor QTY Variants |
| title_full_unstemmed | Comparing Native Crystal Structures and AlphaFold2 Predicted Water-Soluble G Protein-Coupled Receptor QTY Variants |
| title_short | Comparing Native Crystal Structures and AlphaFold2 Predicted Water-Soluble G Protein-Coupled Receptor QTY Variants |
| title_sort | comparing native crystal structures and alphafold2 predicted water soluble g protein coupled receptor qty variants |
| topic | chemokine receptors membrane protein design protein structural predictions QTY code water-soluble GPCRs |
| url | https://www.mdpi.com/2075-1729/11/12/1285 |
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