Thermo-ring basis for heat unfolding-induced inactivation in TRPV1.
| العنوان: | Thermo-ring basis for heat unfolding-induced inactivation in TRPV1. |
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| المؤلفون: | Wang G; Department of Physiology and Membrane Biology, University of California School of Medicine, Davis, CA 95616, USA.; Department of Drug Research and Development, Institute of Biophysical Medico-chemistry, Reno, NV 89523, USA. |
| المصدر: | Research square [Res Sq] 2024 May 09. Date of Electronic Publication: 2024 May 09. |
| نوع المنشور: | Preprint |
| اللغة: | English |
| بيانات الدورية: | Country of Publication: United States NLM ID: 101768035 Publication Model: Electronic Cited Medium: Internet NLM ISO Abbreviation: Res Sq Subsets: PubMed not MEDLINE |
| مستخلص: | Transient receptor potential vanilloid-1 (TRPV1) is a capsaicin receptor and employs the use-dependent desensitization to protect mammals from noxious heat damage in response to repeated or constant heat stimuli. However, the underlying structural factor or motif has not been resolved precisely. In this computational study, the graph theory-based grid thermodynamic model was used to reveal how the temperature-dependent noncovalent interactions as identified in the 3D structures of rat TRPV1 could develop a well-organized fluidic grid-like mesh network, featuring various topological grids constrained as the thermo-rings that range in size from the biggest to the smallest to govern distinct structural and functional traits of the channel in response to varying temperature degrees. Following the findings that the heat unfolding of three specific biggest grids, one in the closed state and two in the open state, was respectively responsible for the reversible activation at 43 °C and thermal inactivation from 56 °C to 61 °C, a random smaller grid was further identified for the irreversible inactivation and the relevant use-dependent desensitization from the pre-open closed state between 43 °C and 61 °C. Thus, these two distinct inactivation pathways of TRPV1 may be involved in protecting mammals against noxious heat damages. Competing Interests: Competing interests The author declares no conflict of interest. |
| References: | Sci Rep. 2016 Aug 09;6:31131. (PMID: 27502553) Nature. 2018 Mar 29;555(7698):662-666. (PMID: 29539642) Elife. 2018 Jun 05;7:. (PMID: 29869983) J Neurosci. 2004 Jun 2;24(22):5177-82. (PMID: 15175387) J Biol Chem. 2004 May 14;279(20):21569-75. (PMID: 15004014) Nat Struct Mol Biol. 2021 Jul;28(7):554-563. (PMID: 34239123) Int J Mol Sci. 2023 Feb 24;24(5):. (PMID: 36901904) Biophys J. 2015 Aug 4;109(3):529-41. (PMID: 26244735) Mol Cell. 2022 Jul 7;82(13):2427-2442.e4. (PMID: 35597238) Molecules. 2023 Feb 15;28(4):. (PMID: 36838836) Biochem Biophys Rep. 2021 Sep 02;28:101109. (PMID: 34504955) Nat Commun. 2020 Aug 20;11(1):4169. (PMID: 32820172) PLoS One. 2015 Jul 21;10(7):e0133550. (PMID: 26197394) J Biol Chem. 2002 Dec 6;277(49):47044-51. (PMID: 12354759) Nat Struct Mol Biol. 2020 Jul;27(7):645-652. (PMID: 32572254) ACS Omega. 2023 Jun 27;8(27):24624-24634. (PMID: 37457467) Pain. 2008 May;136(1-2):202-10. (PMID: 18337008) Sci Rep. 2016 Jul 27;6:28285. (PMID: 27461719) Sci Rep. 2023 Dec 7;13(1):21594. (PMID: 38062125) FASEB J. 2008 Sep;22(9):3298-309. (PMID: 18559878) Int J Biol Macromol. 2023 Sep 1;248:125915. (PMID: 37481175) Nature. 2000 Dec 21-28;408(6815):985-90. (PMID: 11140687) FEBS J. 2016 Jul;283(13):2458-75. (PMID: 27175795) Nature. 2002 Jul 11;418(6894):181-6. (PMID: 12077604) J Neurosci. 2007 Jul 11;27(28):7578-85. (PMID: 17626219) J Biol Chem. 2010 Dec 31;285(53):41455-62. (PMID: 21044960) Sci Rep. 2016 Feb 23;6:22007. (PMID: 26902776) J Biol Chem. 2002 Apr 19;277(16):13375-8. (PMID: 11884385) Nature. 2000 May 11;405(6783):183-7. (PMID: 10821274) Neuron. 1998 Sep;21(3):531-43. (PMID: 9768840) Nat Commun. 2022 May 24;13(1):2874. (PMID: 35610228) Nat Struct Mol Biol. 2021 Jul;28(7):564-572. (PMID: 34239124) Nature. 1997 Oct 23;389(6653):816-24. (PMID: 9349813) ACS Omega. 2023 May 11;8(20):17731-17739. (PMID: 37251155) J Physiol. 2021 Nov;599(21):4831-4844. (PMID: 34605028) Science. 2005 Mar 4;307(5714):1468-72. (PMID: 15746429) Nat Commun. 2019 May 13;10(1):2134. (PMID: 31086183) Protein Sci. 2003 Dec;12(12):2657-67. (PMID: 14627727) J Biol Chem. 2008 Mar 7;283(10):6162-74. (PMID: 18178557) Proc Natl Acad Sci U S A. 2017 Feb 14;114(7):1589-1594. (PMID: 28154143) Proc Natl Acad Sci U S A. 2014 Apr 8;111(14):5213-8. (PMID: 24706910) Nature. 2013 Dec 5;504(7478):107-12. (PMID: 24305160) Proc Natl Acad Sci U S A. 2011 Jul 5;108(27):11109-14. (PMID: 21690353) J Gen Physiol. 2006 Apr;127(4):391-400. (PMID: 16533897) Science. 2002 Jun 14;296(5575):2046-9. (PMID: 12016205) J Gen Physiol. 2011 Nov;138(5):509-20. (PMID: 22006988) J Biol Chem. 2013 Dec 13;288(50):35690-702. (PMID: 24174527) Biophys J. 2003 Nov;85(5):2988-3006. (PMID: 14581201) Proc Natl Acad Sci U S A. 2023 Sep 5;120(36):e2300305120. (PMID: 37639609) |
| معلومات مُعتمدة: | R56 DK045880 United States DK NIDDK NIH HHS; R01 NS032337 United States NS NINDS NIH HHS; R56 DK056796 United States DK NIDDK NIH HHS; R01 DK045880 United States DK NIDDK NIH HHS; T32 AA007463 United States AA NIAAA NIH HHS |
| فهرسة مساهمة: | Keywords: cyclization against decyclization; desensitization; grid thermodynamics; lipid; non-covalent interaction; noxious heat detection; systemic thermal instability; thermoring; thermosensitivity; threshold |
| تواريخ الأحداث: | Date Created: 20230907 Latest Revision: 20240603 |
| رمز التحديث: | 20240603 |
| مُعرف محوري في PubMed: | PMC10479453 |
| DOI: | 10.21203/rs.3.rs-3280283/v2 |
| PMID: | 37674717 |
| قاعدة البيانات: | MEDLINE |
| DOI: | 10.21203/rs.3.rs-3280283/v2 |
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