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Abstract：
Aggregation of the circulating protein leukocyte-cell-derived chemotaxin 2 (LECT2) causes amyloidosis of LECT2 (ALECT2), one of the most prevalent forms of systemic amyloidosis affecting the kidney and liver. The I40V mutation is thought to be necessary but not sufficient for ALECT2, with a second, as-yet undetermined condition being required for the disease. EM, X-ray diffraction, NMR, and fluorescence experiments demonstrate that LECT2 forms amyloid fibrils in vitro in the absence of other proteins. Removal of LECT2\'s single bound Zn2+ appears to be obligatory for fibril formation. Zinc-binding affinity is strongly dependent on pH: 9-13 % of LECT2 is calculated to exist in the zinc-free state over the normal pH range of blood, with this fraction rising to 80 % at pH 6.5. The I40V mutation does not alter zinc-binding affinity or kinetics but destabilizes the zinc-free conformation. These results suggest a mechanism in which loss of zinc together with the I40V mutation leads to ALECT2.
摘要：
循环蛋白白细胞来源的趋化素2（LECT2）的聚集导致LECT2（ALECT2）的淀粉样变性，影响肾脏和肝脏的系统性淀粉样变性的最常见形式之一。I40V突变被认为是必要的，但对于ALECT2来说还不够，该疾病所需的条件尚未确定。EM,X射线衍射,NMR,和荧光实验表明，LECT2在不存在其他蛋白质的情况下在体外形成淀粉样原纤维。去除LECT2的单结合Zn2+似乎是原纤维形成的必要条件。锌结合亲和力强烈依赖于pH：9-13％的LECT2被计算为在血液的正常pH范围内以无锌状态存在，该分数在pH6.5时上升到80%。I40V突变不改变锌结合亲和力或动力学,但使无锌构象不稳定。这些结果表明其中锌的损失与I40V突变一起导致ALECT2的机制。
