Disorder driven allosteric control of protein activity
Studies of protein allostery increasingly reveal an involvement of the back and forth order-disorder transitions in this mechanism of protein activity regulation. Here, we investigate the allosteric mechanisms mediated by structural disorder using the structure-based statistical mechanical model of...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2020-01-01
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| Series: | Current Research in Structural Biology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2665928X20300192 |
| _version_ | 1818647831007723520 |
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| author | Wei-Ven Tee Enrico Guarnera Igor N. Berezovsky |
| author_facet | Wei-Ven Tee Enrico Guarnera Igor N. Berezovsky |
| author_sort | Wei-Ven Tee |
| collection | DOAJ |
| description | Studies of protein allostery increasingly reveal an involvement of the back and forth order-disorder transitions in this mechanism of protein activity regulation. Here, we investigate the allosteric mechanisms mediated by structural disorder using the structure-based statistical mechanical model of allostery (SBSMMA) that we have previously developed. We show that SBSMMA accounts for the energetics and causality of allosteric communication underlying dimerization of the BirA biotin repressor, activation of the sortase A enzyme, and inhibition of the Rac1 GTPase. Using the SBSMMA, we also show that introducing structural order or disorder in various regions of esterases can originate tunable allosteric modulation of the catalytic triad. On the basis of obtained results, we propose that operating with the order-disorder continuum allows one to establish an allosteric control scale for achieving desired modulation of the protein activity. |
| first_indexed | 2024-12-17T01:08:47Z |
| format | Article |
| id | doaj.art-51630aabf736437d861b835a44d1cb4f |
| institution | Directory Open Access Journal |
| issn | 2665-928X |
| language | English |
| last_indexed | 2024-12-17T01:08:47Z |
| publishDate | 2020-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Current Research in Structural Biology |
| spelling | doaj.art-51630aabf736437d861b835a44d1cb4f2022-12-21T22:09:12ZengElsevierCurrent Research in Structural Biology2665-928X2020-01-012191203Disorder driven allosteric control of protein activityWei-Ven Tee0Enrico Guarnera1Igor N. Berezovsky2Bioinformatics Institute (BII), Agency for Science, Technology and Research (A∗STAR), 30 Biopolis Street, #07-01, Matrix 138671, Singapore; Department of Biological Sciences (DBS), National University of Singapore (NUS), 8 Medical Drive 117597, SingaporeBioinformatics Institute (BII), Agency for Science, Technology and Research (A∗STAR), 30 Biopolis Street, #07-01, Matrix 138671, SingaporeBioinformatics Institute (BII), Agency for Science, Technology and Research (A∗STAR), 30 Biopolis Street, #07-01, Matrix 138671, Singapore; Department of Biological Sciences (DBS), National University of Singapore (NUS), 8 Medical Drive 117597, Singapore; Corresponding author. Bioinformatics Institute (BII), Agency for Science, Technology and Research (A∗STAR), 30 Biopolis Street, #07-01, Matrix 138671, Singapore.Studies of protein allostery increasingly reveal an involvement of the back and forth order-disorder transitions in this mechanism of protein activity regulation. Here, we investigate the allosteric mechanisms mediated by structural disorder using the structure-based statistical mechanical model of allostery (SBSMMA) that we have previously developed. We show that SBSMMA accounts for the energetics and causality of allosteric communication underlying dimerization of the BirA biotin repressor, activation of the sortase A enzyme, and inhibition of the Rac1 GTPase. Using the SBSMMA, we also show that introducing structural order or disorder in various regions of esterases can originate tunable allosteric modulation of the catalytic triad. On the basis of obtained results, we propose that operating with the order-disorder continuum allows one to establish an allosteric control scale for achieving desired modulation of the protein activity.http://www.sciencedirect.com/science/article/pii/S2665928X20300192Protein allosteryProtein intrinsic disorderOrder-disorder transitionsAllosteric modulationAllosteric free energyAllosteric control scale |
| spellingShingle | Wei-Ven Tee Enrico Guarnera Igor N. Berezovsky Disorder driven allosteric control of protein activity Current Research in Structural Biology Protein allostery Protein intrinsic disorder Order-disorder transitions Allosteric modulation Allosteric free energy Allosteric control scale |
| title | Disorder driven allosteric control of protein activity |
| title_full | Disorder driven allosteric control of protein activity |
| title_fullStr | Disorder driven allosteric control of protein activity |
| title_full_unstemmed | Disorder driven allosteric control of protein activity |
| title_short | Disorder driven allosteric control of protein activity |
| title_sort | disorder driven allosteric control of protein activity |
| topic | Protein allostery Protein intrinsic disorder Order-disorder transitions Allosteric modulation Allosteric free energy Allosteric control scale |
| url | http://www.sciencedirect.com/science/article/pii/S2665928X20300192 |
| work_keys_str_mv | AT weiventee disorderdrivenallostericcontrolofproteinactivity AT enricoguarnera disorderdrivenallostericcontrolofproteinactivity AT igornberezovsky disorderdrivenallostericcontrolofproteinactivity |