Diverse single-stranded nucleic acid binding proteins enable both stable protection and rapid exchange required for biological function
Single-stranded nucleic acid (ssNA) binding proteins must both stably protect ssNA transiently exposed during replication and other NA transactions, and also rapidly reorganize and dissociate to allow further NA processing. How these seemingly opposing functions can coexist has been recently elucida...
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| Language: | English |
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Cambridge University Press
2025-01-01
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| Series: | QRB Discovery |
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| Online Access: | https://www.cambridge.org/core/product/identifier/S2633289224000218/type/journal_article |
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| author | Michael Morse Ben A. Cashen Ioulia Rouzina Mark C. Williams |
| author_facet | Michael Morse Ben A. Cashen Ioulia Rouzina Mark C. Williams |
| author_sort | Michael Morse |
| collection | DOAJ |
| description | Single-stranded nucleic acid (ssNA) binding proteins must both stably protect ssNA transiently exposed during replication and other NA transactions, and also rapidly reorganize and dissociate to allow further NA processing. How these seemingly opposing functions can coexist has been recently elucidated by optical tweezers (OT) experiments that isolate and manipulate single long ssNA molecules to measure conformation in real time. The effective length of an ssNA substrate held at fixed tension is altered upon protein binding, enabling quantification of both the structure and kinetics of protein–NA interactions. When proteins exhibit multiple binding states, however, OT measurements may produce difficult to analyze signals including non-monotonic response to free protein concentration and convolution of multiple fundamental rates. In this review we compare single-molecule experiments with three proteins of vastly different structure and origin that exhibit similar ssNA interactions. These results are consistent with a general model in which protein oligomers containing multiple binding interfaces switch conformations to adjust protein:NA stoichiometry. These characteristics allow a finite number of proteins to protect long ssNA regions by maximizing protein–ssNA contacts while also providing a pathway with reduced energetic barriers to reorganization and eventual protein displacement when these ssNA regions are diminished. |
| format | Article |
| id | doaj-art-d0291da9626a40f38568cceda71590d7 |
| institution | Kabale University |
| issn | 2633-2892 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Cambridge University Press |
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| series | QRB Discovery |
| spelling | doaj-art-d0291da9626a40f38568cceda71590d72025-02-04T04:09:43ZengCambridge University PressQRB Discovery2633-28922025-01-01610.1017/qrd.2024.21Diverse single-stranded nucleic acid binding proteins enable both stable protection and rapid exchange required for biological functionMichael Morse0Ben A. Cashen1Ioulia Rouzina2Mark C. Williams3https://orcid.org/0000-0003-3219-376XDepartment of Physics, Northeastern University, Boston, MA, USADepartment of Physics, Northeastern University, Boston, MA, USADepartment of Chemistry and Biochemistry, Ohio State University, Columbus, OH, USADepartment of Physics, Northeastern University, Boston, MA, USASingle-stranded nucleic acid (ssNA) binding proteins must both stably protect ssNA transiently exposed during replication and other NA transactions, and also rapidly reorganize and dissociate to allow further NA processing. How these seemingly opposing functions can coexist has been recently elucidated by optical tweezers (OT) experiments that isolate and manipulate single long ssNA molecules to measure conformation in real time. The effective length of an ssNA substrate held at fixed tension is altered upon protein binding, enabling quantification of both the structure and kinetics of protein–NA interactions. When proteins exhibit multiple binding states, however, OT measurements may produce difficult to analyze signals including non-monotonic response to free protein concentration and convolution of multiple fundamental rates. In this review we compare single-molecule experiments with three proteins of vastly different structure and origin that exhibit similar ssNA interactions. These results are consistent with a general model in which protein oligomers containing multiple binding interfaces switch conformations to adjust protein:NA stoichiometry. These characteristics allow a finite number of proteins to protect long ssNA regions by maximizing protein–ssNA contacts while also providing a pathway with reduced energetic barriers to reorganization and eventual protein displacement when these ssNA regions are diminished.https://www.cambridge.org/core/product/identifier/S2633289224000218/type/journal_articleoptical tweezersprotein–nucleic acid interactionssingle molecule biophysics |
| spellingShingle | Michael Morse Ben A. Cashen Ioulia Rouzina Mark C. Williams Diverse single-stranded nucleic acid binding proteins enable both stable protection and rapid exchange required for biological function QRB Discovery optical tweezers protein–nucleic acid interactions single molecule biophysics |
| title | Diverse single-stranded nucleic acid binding proteins enable both stable protection and rapid exchange required for biological function |
| title_full | Diverse single-stranded nucleic acid binding proteins enable both stable protection and rapid exchange required for biological function |
| title_fullStr | Diverse single-stranded nucleic acid binding proteins enable both stable protection and rapid exchange required for biological function |
| title_full_unstemmed | Diverse single-stranded nucleic acid binding proteins enable both stable protection and rapid exchange required for biological function |
| title_short | Diverse single-stranded nucleic acid binding proteins enable both stable protection and rapid exchange required for biological function |
| title_sort | diverse single stranded nucleic acid binding proteins enable both stable protection and rapid exchange required for biological function |
| topic | optical tweezers protein–nucleic acid interactions single molecule biophysics |
| url | https://www.cambridge.org/core/product/identifier/S2633289224000218/type/journal_article |
| work_keys_str_mv | AT michaelmorse diversesinglestrandednucleicacidbindingproteinsenablebothstableprotectionandrapidexchangerequiredforbiologicalfunction AT benacashen diversesinglestrandednucleicacidbindingproteinsenablebothstableprotectionandrapidexchangerequiredforbiologicalfunction AT iouliarouzina diversesinglestrandednucleicacidbindingproteinsenablebothstableprotectionandrapidexchangerequiredforbiologicalfunction AT markcwilliams diversesinglestrandednucleicacidbindingproteinsenablebothstableprotectionandrapidexchangerequiredforbiologicalfunction |