Equilibrium between monomers and dimers of the death domain of the p75 neurotrophin receptor in solution
Equilibrium between monomers and dimers of the death domain of the p75 neurotrophin receptor in solution
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DOI：
10.1016/j.ijbiomac.2023.125710
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发表时间：
2023-07-07
影响因子：
8.2
通讯作者：
Lin，Zhi
中科院分区：
文献类型：
--
作者：
Li，Zhen;Duan，Yajing;Lin，Zhi
p75神经营养蛋白受体（p75 NTR）包含一个C末端球状蛋白模块，称为死亡结构域（DD），它通过形成寡聚蛋白复合物在细胞凋亡和炎症信号传导中发挥核心作用。p75 NTR-DD的单体状态也取决于其体外化学修饰而存在。然而，对p75 NTR-DD寡聚状态的研究产生了相互矛盾的结果，并引发了巨大的争议。在这里，我们提出了新的证据，从生物物理和生物化学的研究，以证明对称和不对称的p75 NTR-DD，这可能是平衡的单体形式在溶液中，在没有任何其他蛋白质的二聚体的共存。可逆的闭-开溶液行为对于p75 NTR-DD作为细胞内信号传导枢纽可能是重要的。这一结果支持了p75 NTR-DD自缔合的内在能力，与DD超家族所有成员的寡聚化性质一致。
p75 neurotrophin receptor (p75NTR) contains a C-terminal globular protein module known as the death domain (DD), which plays a central role in apoptotic and inflammatory signaling through the formation of oligomeric protein complexes. A monomeric state of the p75NTR-DD also exists depending on its chemical environmentin vitro. However, studies on the oligomeric states of the p75NTR-DD have produced conflicting findings and sparked great controversy. Here we present new evidence from biophysical and biochemical studies to demonstrate the coexistence of symmetric and asymmetric dimers of the p75NTR-DD, which may equilibrate with the monomeric form in solution and in the absence of any other protein. The reversible close-open solution behavior may be important for the p75NTR-DD to serve as an intracellular signaling hub. This result supports an intrinsic ability of the p75NTR-DD to self-associate, in congruence with the oligomerization properties of all members of the DD superfamily.