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hybrid
·인용수 1
·2025
Functional unfolding of the integrin αX transmembrane helix
Han Vu, Minhyeong Lee, Alan J. Situ, Woojin An, Klaus Ley, Chungho Kim, Tobias S. Ulmer
IF 9.1Proceedings of the National Academy of Sciences
초록

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.

키워드
Transmembrane domainIntegrinHelix (gastropod)Transmembrane proteinAlpha helixMembrane proteinCollagen helixMembraneProtein structure
타입
article
IF / 인용수
9.1 / 1
게재 연도
2025