期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 109, 期 28, 页码 11188-11193出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1118120109
关键词
heterogeneous crystal nucleation; beta-hematin; X-ray microscopy; focused ion beam; quinoline
资金
- Clore Center for Biological Physics
- European Community [226716]
Heme detoxification is a critical step in the life cycle of malaria-causing parasites, achieved by crystallization into physiologically insoluble hemozoin. The mode of nucleation has profound implications for understanding the mechanism of action of antimalarial drugs that inhibit hemozoin growth. Several lines of evidence point to involvement of acylglycerol lipids in the nucleation process. Hemozoin crystals have been reported to form within lipid nanospheres; alternatively, it has been found in vitro that they are nucleated at an acylglycerol lipid-water interface. We have applied cryogenic soft X-ray tomography and three-dimensional electron microscopy to address the location and orientation of hemozoin crystals within the digestive vacuole (DV), as a signature of their nucleation and growth processes. Cryogenic soft X-ray tomography in the water window is particularly advantageous because contrast generation is based inherently on atomic absorption. We find that hemozoin nucleation occurs at the DV inner membrane, with crystallization occurring in the aqueous rather than lipid phase. The crystal morphology indicates a common {100} orientation facing the membrane as expected of templated nucleation. This is consistent with conclusions reached by X-ray fluorescence and diffraction in a companion work. Uniform dark spheres observed in the parasite were identified as hemoglobin transport vesicles. Their analysis supports a model of hemozoin nucleation primarily in the DV. Modeling of the contrast at the DV membrane indicates a 4-nm thickness with patches about three times thicker, possibly implicated in the nucleation.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据