New Horizons in Structural Biology of Membrane Proteins: Experimental Evaluation of the Role of Conformational Dynamics and Intrinsic Flexibility
A plethora of membrane proteins are found along the cell surface and on the convoluted labyrinth of membranes surrounding organelles. Since the advent of various structural biology techniques, a sub-population of these proteins has become accessible to investigation at near-atomic resolutions. The p...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-02-01
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| Series: | Membranes |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2077-0375/12/2/227 |
| _version_ | 1827654030558494720 |
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| author | Robbins Puthenveetil Eric T. Christenson Olga Vinogradova |
| author_facet | Robbins Puthenveetil Eric T. Christenson Olga Vinogradova |
| author_sort | Robbins Puthenveetil |
| collection | DOAJ |
| description | A plethora of membrane proteins are found along the cell surface and on the convoluted labyrinth of membranes surrounding organelles. Since the advent of various structural biology techniques, a sub-population of these proteins has become accessible to investigation at near-atomic resolutions. The predominant bona fide methods for structure solution, X-ray crystallography and cryo-EM, provide high resolution in three-dimensional space at the cost of neglecting protein motions through time. Though structures provide various rigid snapshots, only an amorphous mechanistic understanding can be inferred from interpolations between these different static states. In this review, we discuss various techniques that have been utilized in observing dynamic conformational intermediaries that remain elusive from rigid structures. More specifically we discuss the application of structural techniques such as NMR, cryo-EM and X-ray crystallography in studying protein dynamics along with complementation by conformational trapping by specific binders such as antibodies. We finally showcase the strength of various biophysical techniques including FRET, EPR and computational approaches using a multitude of succinct examples from GPCRs, transporters and ion channels. |
| first_indexed | 2024-03-09T21:27:49Z |
| format | Article |
| id | doaj.art-aaa98161ff88485eb691028fc448f2e1 |
| institution | Directory Open Access Journal |
| issn | 2077-0375 |
| language | English |
| last_indexed | 2024-03-09T21:27:49Z |
| publishDate | 2022-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Membranes |
| spelling | doaj.art-aaa98161ff88485eb691028fc448f2e12023-11-23T21:03:53ZengMDPI AGMembranes2077-03752022-02-0112222710.3390/membranes12020227New Horizons in Structural Biology of Membrane Proteins: Experimental Evaluation of the Role of Conformational Dynamics and Intrinsic FlexibilityRobbins Puthenveetil0Eric T. Christenson1Olga Vinogradova2Section on Structural and Chemical Biology of Membrane Proteins, Neurosciences and Cellular and Structural Biology Division, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, 35A Convent Dr., Bethesda, MD 20892, USAOriGene Technologies, Inc., Rockville, MD 20850, USADepartment of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut, Storrs, CT 06269, USAA plethora of membrane proteins are found along the cell surface and on the convoluted labyrinth of membranes surrounding organelles. Since the advent of various structural biology techniques, a sub-population of these proteins has become accessible to investigation at near-atomic resolutions. The predominant bona fide methods for structure solution, X-ray crystallography and cryo-EM, provide high resolution in three-dimensional space at the cost of neglecting protein motions through time. Though structures provide various rigid snapshots, only an amorphous mechanistic understanding can be inferred from interpolations between these different static states. In this review, we discuss various techniques that have been utilized in observing dynamic conformational intermediaries that remain elusive from rigid structures. More specifically we discuss the application of structural techniques such as NMR, cryo-EM and X-ray crystallography in studying protein dynamics along with complementation by conformational trapping by specific binders such as antibodies. We finally showcase the strength of various biophysical techniques including FRET, EPR and computational approaches using a multitude of succinct examples from GPCRs, transporters and ion channels.https://www.mdpi.com/2077-0375/12/2/227membrane proteinsmembrane protein structuremembrane protein dynamicsNMRcryo-EMX-ray |
| spellingShingle | Robbins Puthenveetil Eric T. Christenson Olga Vinogradova New Horizons in Structural Biology of Membrane Proteins: Experimental Evaluation of the Role of Conformational Dynamics and Intrinsic Flexibility Membranes membrane proteins membrane protein structure membrane protein dynamics NMR cryo-EM X-ray |
| title | New Horizons in Structural Biology of Membrane Proteins: Experimental Evaluation of the Role of Conformational Dynamics and Intrinsic Flexibility |
| title_full | New Horizons in Structural Biology of Membrane Proteins: Experimental Evaluation of the Role of Conformational Dynamics and Intrinsic Flexibility |
| title_fullStr | New Horizons in Structural Biology of Membrane Proteins: Experimental Evaluation of the Role of Conformational Dynamics and Intrinsic Flexibility |
| title_full_unstemmed | New Horizons in Structural Biology of Membrane Proteins: Experimental Evaluation of the Role of Conformational Dynamics and Intrinsic Flexibility |
| title_short | New Horizons in Structural Biology of Membrane Proteins: Experimental Evaluation of the Role of Conformational Dynamics and Intrinsic Flexibility |
| title_sort | new horizons in structural biology of membrane proteins experimental evaluation of the role of conformational dynamics and intrinsic flexibility |
| topic | membrane proteins membrane protein structure membrane protein dynamics NMR cryo-EM X-ray |
| url | https://www.mdpi.com/2077-0375/12/2/227 |
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