Pressure, motion, and conformational entropy in molecular recognition by proteins
The thermodynamics of molecular recognition by proteins is a central determinant of complex biochemistry. For over a half-century, detailed cryogenic structures have provided deep insight into the energetic contributions to ligand binding by proteins. More recently, a dynamical proxy based on NMR-re...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-03-01
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| Series: | Biophysical Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2667074722000556 |
| _version_ | 1797956171472044032 |
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| author | José A. Caro Kathleen G. Valentine Taylor R. Cole A. Joshua Wand |
| author_facet | José A. Caro Kathleen G. Valentine Taylor R. Cole A. Joshua Wand |
| author_sort | José A. Caro |
| collection | DOAJ |
| description | The thermodynamics of molecular recognition by proteins is a central determinant of complex biochemistry. For over a half-century, detailed cryogenic structures have provided deep insight into the energetic contributions to ligand binding by proteins. More recently, a dynamical proxy based on NMR-relaxation methods has revealed an unexpected richness in the contributions of conformational entropy to the thermodynamics of ligand binding. Here, we report the pressure dependence of fast internal motion within the ribonuclease barnase and its complex with the protein barstar. In what we believe is a first example, we find that protein dynamics are conserved along the pressure-binding thermodynamic cycle. The femtomolar affinity of the barnase-barstar complex exists despite a penalty by −TΔSconf of +11.7 kJ/mol at ambient pressure. At high pressure, however, the overall change in side-chain dynamics is zero, and binding occurs with no conformational entropy penalty, suggesting an important role of conformational dynamics in the adaptation of protein function to extreme environments. Distinctive clustering of the pressure sensitivity is observed in response to both pressure and binding, indicating the presence of conformational heterogeneity involving less efficiently packed alternative conformation(s). The structural segregation of dynamics observed in barnase is striking and shows how changes in both the magnitude and the sign of regional contributions of conformational entropy to the thermodynamics of protein function are possible. |
| first_indexed | 2024-04-10T23:45:53Z |
| format | Article |
| id | doaj.art-69eae41ec89b401abf3ade8765988f6c |
| institution | Directory Open Access Journal |
| issn | 2667-0747 |
| language | English |
| last_indexed | 2024-04-10T23:45:53Z |
| publishDate | 2023-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biophysical Reports |
| spelling | doaj.art-69eae41ec89b401abf3ade8765988f6c2023-01-11T04:30:28ZengElsevierBiophysical Reports2667-07472023-03-0131100098Pressure, motion, and conformational entropy in molecular recognition by proteinsJosé A. Caro0Kathleen G. Valentine1Taylor R. Cole2A. Joshua Wand3Department of Biochemistry & Biophysics, Texas A&M University, College Station, TexasDepartment of Biochemistry & Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PennsylvaniaDepartment of Biochemistry & Biophysics, Texas A&M University, College Station, TexasDepartment of Biochemistry & Biophysics, Texas A&M University, College Station, Texas; Department of Molecular & Cellular Medicine, Texas A&M University, College Station, Texas; Department of Chemistry, Texas A&M University, College Station, Texas; Department of Biochemistry & Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; Corresponding authorThe thermodynamics of molecular recognition by proteins is a central determinant of complex biochemistry. For over a half-century, detailed cryogenic structures have provided deep insight into the energetic contributions to ligand binding by proteins. More recently, a dynamical proxy based on NMR-relaxation methods has revealed an unexpected richness in the contributions of conformational entropy to the thermodynamics of ligand binding. Here, we report the pressure dependence of fast internal motion within the ribonuclease barnase and its complex with the protein barstar. In what we believe is a first example, we find that protein dynamics are conserved along the pressure-binding thermodynamic cycle. The femtomolar affinity of the barnase-barstar complex exists despite a penalty by −TΔSconf of +11.7 kJ/mol at ambient pressure. At high pressure, however, the overall change in side-chain dynamics is zero, and binding occurs with no conformational entropy penalty, suggesting an important role of conformational dynamics in the adaptation of protein function to extreme environments. Distinctive clustering of the pressure sensitivity is observed in response to both pressure and binding, indicating the presence of conformational heterogeneity involving less efficiently packed alternative conformation(s). The structural segregation of dynamics observed in barnase is striking and shows how changes in both the magnitude and the sign of regional contributions of conformational entropy to the thermodynamics of protein function are possible.http://www.sciencedirect.com/science/article/pii/S2667074722000556 |
| spellingShingle | José A. Caro Kathleen G. Valentine Taylor R. Cole A. Joshua Wand Pressure, motion, and conformational entropy in molecular recognition by proteins Biophysical Reports |
| title | Pressure, motion, and conformational entropy in molecular recognition by proteins |
| title_full | Pressure, motion, and conformational entropy in molecular recognition by proteins |
| title_fullStr | Pressure, motion, and conformational entropy in molecular recognition by proteins |
| title_full_unstemmed | Pressure, motion, and conformational entropy in molecular recognition by proteins |
| title_short | Pressure, motion, and conformational entropy in molecular recognition by proteins |
| title_sort | pressure motion and conformational entropy in molecular recognition by proteins |
| url | http://www.sciencedirect.com/science/article/pii/S2667074722000556 |
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