Transthyretin/TTR 蛋白, Human (127a.a, HEK293, His)

Transthyretin (TTR) belongs to the serum transporter family and is a plasma transporter of T₄ and retinol. Transthyretin inhibits Aβ_1-42 fibrillization and is a potential target for amyloidosis and Alzheimer's disease. Transthyretin mutations (such as V30M) can destabilize the tetramer and promote the formation of amyloid fibrils in monomers, causing hereditary amyloidosis transthyretin (ATTRv). Transthyretin/TTR Protein, Human (127a.a, HEK293, His) is a recombinant transthyretin/TTR protein expressed in HEK293 with a C-6*His tag.

1. Transthyretin/TTR 的蛋白特点
Transthyretin (TTR) 是通过二硫键连接的同源四聚体，含保守的 β-折叠结构及两个甲状腺素 (T₄) 结合位点。Transthyretin/TTR 需经信号肽切割后形成成熟蛋白，通过 T₄ 结合维持四聚体稳定性^[1]。Transthyretin/TTR 属于血清转运蛋白家族，是 T₄ 和视黄醇的血浆运输载体，与视黄醇结合蛋白形成复合物，介导维生素 A 运输，维持甲状腺激素和维生素 A 的稳态^[2]。而突变 (如 V30M、L55P)，可破坏 Transthyretin/TTR 四聚体稳定性，促使单体解离并自组装为 β-片层纤维，沉积于神经、心脏等组织引发遗传性转甲状腺素蛋白淀粉样变性 (ATTRv)。非纤维寡聚体通过钙内流及内质网应激导致细胞毒性^[1]。
Transthyretin/TTR 与 Aβ_1-42 结合，通过 T₄ 结合口袋抑制其纤维化，延缓阿尔茨海默病相关病理^[2]。或 Transthyretin/TTR 与糖胺聚糖等内源性因子协同促进淀粉样沉积^[1]。

2. Transthyretin/TTR 的应用
Transthyretin/TTR 可用于淀粉样变性疾病 ATTRv 的病理机制研究。如构建突变体 (如 L55P) 转基因小鼠用于药物筛选，研究 Transthyretin/TTR 稳定剂，如 Diflunisal 通过稳定 Transthyretin/TTR 四聚体延缓淀粉样纤维形成^[3]；同时，稳定剂 Tafamidis 已被证实可用于抑制 ATTRv 神经病^[1]。Transthyretin/TTRR 靶向 Aβ 聚集，是阿尔茨海默病的潜在靶点^[2]。

Transthyretin/TTR Protein (人源 huTTR；0.25-2 μM) 在硫黄素 T (ThT，20 μM) 荧光测定中抑制 Aβ_1-40 聚合纤维 (10 μM) 形成，其中突变体 M-TTR (F87M/L110M) 抑制效果最强，WT huTTR 次之，鼠源 muTTR 最弱^[2]。
Transthyretin/TTR Protein (人源 huTTR；2.5 μM；5 d) 抑制 Aβ_1-42 的纤维和寡聚体形成，突变体 M-TTR 处理组无明显纤维结构，huTTR 组纤维数量减少，muTTR 组无显著抑制^[2]。
Transthyretin/TTR Protein (人源 huTTR；20 μM；3 min) 与固定化 Aβ_1-40 单体结合，结合强度排序为 M-TTR＞V30M TTR≥WT huTTR＞V122I TTR^[2]。
Transthyretin/TTR Protein (

Measured by its binding ability in a functional ELISA. Immobilized recombinant human TTR-His at 10 μg/ml (100 μl/well) can bind recombinant Canine RBP4-Fc with a linear range of 0.3-10.0 μg/ml.

Human

HEK293

C-6*His

P02766 (G21-E147)

7276  [NCBI]

Full Length of Mature Protein

GPTGTGESKCPLMVKVLDAVRGSPAINVAVHVFRKAADDTWEPFASGKTSESGELHGLTTEEEFVEGIYKVEIDTKSYWKALGISPFHEHAEVVFTANDSGPRRYTIAALLSPYSYSTTAVVTNPKE

Approximately 18 kDa, based on SDS-PAGE under reducing conditions, due to the glycosylation.

• 
  Greater than 95% as determined by reducing SDS-PAGE.

无菌粉末.

1.Lyophilized from a 0.22 μm filtered solution of 20 mM Tris-HCl, 150 mM NaCl, pH 8.0.
2.Lyophilized from a 0.22 μm filtered solution of 20 mM PB, 150 mM NaCl, pH 7.8.
3.Lyophilized from a 0.22 μm filtered solution of PBS, pH 7.4, 5% trehalose, 5% mannitol and 0.01% Tween 80.
4.Lyophilized from a 0.22 μm filtered solution of PBS, pH 7.4, 8% trehalose.

<1 EU/μg, determined by LAL method.

It is not recommended to reconstitute to a concentration less than 100 μg/mL in ddH₂O. For long term storage it is recommended to add a carrier protein (0.1% BSA, 5% HSA, 10% FBS or 5% Trehalose).

Stored at -20°C for 2 years from date of receipt. After reconstitution, it is stable at 4°C for 1 week or -20°C for longer (with carrier protein). It is recommended to freeze aliquots at -20°C or -80°C for extended storage.

Room temperature in continental US; may vary elsewhere.

• [1]. Manganelli F, et al. Hereditary transthyretin amyloidosis overview. Neurol Sci. 2022 Dec;43(Suppl 2):595-604.  [Content Brief]

  [2]. Li X, et al. Mechanisms of transthyretin inhibition of β-amyloid aggregation in vitro. J Neurosci. 2013 Dec 11;33(50):19423-33.  [Content Brief]

  [3]. Tagoe CE, et al. In vivo stabilization of mutant human transthyretin in transgenic mice. Amyloid. 2007 Sep;14(3):227-36.  [Content Brief]