Comparison of Integrin αIIbβ3 Transmembrane Association in Vesicles and Bicelles.

Comparison of Integrin αIIbβ3 Transmembrane Association in Vesicles and Bicelles.
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囊泡和 Bicelles 中整合素 αIIbβ3 跨膜关联的比较。

DOI:
10.1021/acs.biochem.3c00177
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发表时间:
2023
期刊:
影响因子:
2.9
通讯作者:
Ulmer,TobiasS
Ulmer,TobiasS
中科院分区:
生物学3区
文献类型:
--
作者:
Situ,AlanJ;Ulmer,TobiasS

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膜蛋白通常以膜模拟物的形式重组,呈现不连续的脂双层结构。相反,连续的细胞膜在概念上以大的单层囊泡(LuV)最好地代表。在这里,我们比较了整合素αIIbβ3跨膜(TM)复合体在囊泡和双囊泡之间的热力学稳定性,以评估这一简化的结果。在LuV中,我们进一步评估了αIIb(G972S)-β3(V700T)相互作用的强度,该相互作用对应于β2整合素假设的氢键相互作用。相对于双细胞,LUV中TM复合体的稳定性上限估计为0.9kcal/mol。与αIIbβ3 TM复合体在肺组织中的稳定性5.6±0.2千卡/摩尔相比,这一限制是适度的,表明双细胞相对于肺组织表现良好。β3(V700T)的实施缓解了αIIb(G972S)的失稳,降低了0.4±0.2千卡/摩尔,证实了相对较弱的氢键。有趣的是,氢键将TM复合体的稳定性调节到了仅通过改变与αIIb(Gly972)对应的残基所不能达到的水平。
Membrane proteins are commonly reconstituted in membrane mimics exhibiting discontinuous lipid bilayers. In contrast, the continuous membranes of cells are conceptually best represented by large unilamellar vesicles (LUVs). Here, we compared the thermodynamic stability of the integrin αIIbβ3 transmembrane (TM) complex between vesicles and bicelles to assess the consequence of this simplification. In LUVs, we further evaluated the strength of the αIIb(G972S)-β3(V700T) interaction that corresponds to the hydrogen bond interaction postulated for β2 integrins. An upper limit of 0.9 kcal/mol was estimated for superior TM complex stabilization in LUVs relative to bicelles. Compared to the αIIbβ3 TM complex stability in LUVs of 5.6 ± 0.2 kcal/mol, this limit is modest, indicating that bicelles performed well relative to LUVs. The implementation of β3(V700T) alleviated αIIb(G972S) destabilization by 0.4 ± 0.2 kcal/mol in confirmation of relatively weak hydrogen bonding. Interestingly, the hydrogen bond adjusts the TM complex stability to a level that is not achievable by merely varying the residue corresponding to αIIb(Gly972).
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发表时间: 2018
期刊: The journal of physical chemistry. B
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