Functional unfolding of the integrin αX transmembrane helix.
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| Title: | Functional unfolding of the integrin αX transmembrane helix. |
|---|---|
| Authors: | Vu, Han N.1, Lee, Minhyeong2, Situ, Alan J.1, An, Woojin3, Ley, Klaus4, Kim, Chungho2 chungho@korea.ac.kr, Ulmer, Tobias S.1 tulmer@usc.edu |
| Source: | Proceedings of the National Academy of Sciences of the United States of America. 9/23/2025, Vol. 122 Issue 38, p1-9. 9p. |
| Subjects: | Integrins, Cell adhesion, Bilayer lipid membranes, Denaturation of proteins, Physiology, Phagocytosis, Hydrogen bonding |
| Abstract: | In biological membranes, proteins face a fundamentally different environment than in water. To avoid untenable lipid contacts with polar backbone atoms, they use the continuous hydrogen bonding achieved by α-helices or β-barrels to traverse membranes. Here, we show that integrin αX, and by homology αM, undermine this paradigm by partially unfolding the N-terminal third of their transmembrane (TM) helix. Unfolding results in a dynamic, frayed helix that weakens the association with its partnering β2 subunit to lower the activation threshold of integrin αXβ2-mediated cell adhesion. The extent of unfolding depends on membrane geometry, thereby establishing a mechanism for sensing membrane properties. The combination of adhesive control with sensory capacity in integrin αXβ2 and αMβ2 may achieve membrane localization-dependent receptor activation in leukocyte phagocytosis. The unfolding of the αX TM helix arises from a high number of α-helix-destabilizing residues that TM helices in general approach but do not exceed. Accordingly, backbone dynamics of TM helices may disrupt hydrogen bonds, modulate protein function, and optimize TM helix rigidity. [ABSTRACT FROM AUTHOR] |
| Copyright of Proceedings of the National Academy of Sciences of the United States of America is the property of National Academy of Sciences and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) | |
| Database: | Engineering Source |
| FullText | Text: Availability: 0 |
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| Header | DbId: egs DbLabel: Engineering Source An: 188342707 AccessLevel: 6 PubType: Academic Journal PubTypeId: academicJournal PreciseRelevancyScore: 0 |
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| Items | – Name: Title Label: Title Group: Ti Data: Functional unfolding of the integrin αX transmembrane helix. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Vu%2C+Han+N%2E%22">Vu, Han N.</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Lee%2C+Minhyeong%22">Lee, Minhyeong</searchLink><relatesTo>2</relatesTo><br /><searchLink fieldCode="AR" term="%22Situ%2C+Alan+J%2E%22">Situ, Alan J.</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22An%2C+Woojin%22">An, Woojin</searchLink><relatesTo>3</relatesTo><br /><searchLink fieldCode="AR" term="%22Ley%2C+Klaus%22">Ley, Klaus</searchLink><relatesTo>4</relatesTo><br /><searchLink fieldCode="AR" term="%22Kim%2C+Chungho%22">Kim, Chungho</searchLink><relatesTo>2</relatesTo><i> chungho@korea.ac.kr</i><br /><searchLink fieldCode="AR" term="%22Ulmer%2C+Tobias+S%2E%22">Ulmer, Tobias S.</searchLink><relatesTo>1</relatesTo><i> tulmer@usc.edu</i> – Name: TitleSource Label: Source Group: Src Data: <searchLink fieldCode="JN" term="%22Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America%22">Proceedings of the National Academy of Sciences of the United States of America</searchLink>. 9/23/2025, Vol. 122 Issue 38, p1-9. 9p. – Name: Subject Label: Subjects Group: Su Data: <searchLink fieldCode="DE" term="%22Integrins%22">Integrins</searchLink><br /><searchLink fieldCode="DE" term="%22Cell+adhesion%22">Cell adhesion</searchLink><br /><searchLink fieldCode="DE" term="%22Bilayer+lipid+membranes%22">Bilayer lipid membranes</searchLink><br /><searchLink fieldCode="DE" term="%22Denaturation+of+proteins%22">Denaturation of proteins</searchLink><br /><searchLink fieldCode="DE" term="%22Physiology%22">Physiology</searchLink><br /><searchLink fieldCode="DE" term="%22Phagocytosis%22">Phagocytosis</searchLink><br /><searchLink fieldCode="DE" term="%22Hydrogen+bonding%22">Hydrogen bonding</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: In biological membranes, proteins face a fundamentally different environment than in water. To avoid untenable lipid contacts with polar backbone atoms, they use the continuous hydrogen bonding achieved by α-helices or β-barrels to traverse membranes. Here, we show that integrin αX, and by homology αM, undermine this paradigm by partially unfolding the N-terminal third of their transmembrane (TM) helix. Unfolding results in a dynamic, frayed helix that weakens the association with its partnering β2 subunit to lower the activation threshold of integrin αXβ2-mediated cell adhesion. The extent of unfolding depends on membrane geometry, thereby establishing a mechanism for sensing membrane properties. The combination of adhesive control with sensory capacity in integrin αXβ2 and αMβ2 may achieve membrane localization-dependent receptor activation in leukocyte phagocytosis. The unfolding of the αX TM helix arises from a high number of α-helix-destabilizing residues that TM helices in general approach but do not exceed. Accordingly, backbone dynamics of TM helices may disrupt hydrogen bonds, modulate protein function, and optimize TM helix rigidity. [ABSTRACT FROM AUTHOR] – Name: AbstractSuppliedCopyright Label: Group: Ab Data: <i>Copyright of Proceedings of the National Academy of Sciences of the United States of America is the property of National Academy of Sciences and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.) |
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| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.1073/pnas.2507966122 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 9 StartPage: 1 Subjects: – SubjectFull: Integrins Type: general – SubjectFull: Cell adhesion Type: general – SubjectFull: Bilayer lipid membranes Type: general – SubjectFull: Denaturation of proteins Type: general – SubjectFull: Physiology Type: general – SubjectFull: Phagocytosis Type: general – SubjectFull: Hydrogen bonding Type: general Titles: – TitleFull: Functional unfolding of the integrin αX transmembrane helix. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Vu, Han N. – PersonEntity: Name: NameFull: Lee, Minhyeong – PersonEntity: Name: NameFull: Situ, Alan J. – PersonEntity: Name: NameFull: An, Woojin – PersonEntity: Name: NameFull: Ley, Klaus – PersonEntity: Name: NameFull: Kim, Chungho – PersonEntity: Name: NameFull: Ulmer, Tobias S. IsPartOfRelationships: – BibEntity: Dates: – D: 23 M: 09 Text: 9/23/2025 Type: published Y: 2025 Identifiers: – Type: issn-print Value: 00278424 Numbering: – Type: volume Value: 122 – Type: issue Value: 38 Titles: – TitleFull: Proceedings of the National Academy of Sciences of the United States of America Type: main |
| ResultId | 1 |
