Institute of Biological Information Processing, IBI-7: Structural Biochemistry, Forschungszentrum Jülich, 52425 Jülich, Germany.
Klinik für Dermatologie, Universitätsklinikum Düsseldorf, 40225 Düsseldorf, Germany.
Biomolecules. 2022 Oct 28;12(11):1588. doi: 10.3390/biom12111588.
Human C-C motif ligand 16 (CCL16) is a chemokine that is distinguished by a large cleavable C-terminal extension of unknown significance. Conflicting data have been reported concerning its tissue distribution and modulation of expression, rendering the biological function of CCL16 enigmatic. Here, we report an integrated approach to the characterisation of this chemokine, including a re-assessment of its expression characteristics as well as a biophysical investigation with respect to its structure and dynamics. Our data indicate that CCL16 is chiefly synthesised by hepatocytes, without an appreciable response to mediators of inflammation, and circulates in the blood as a full-length protein. While the crystal structure of CCL16 confirms the presence of a canonical chemokine domain, molecular dynamics simulations support the view that the C-terminal extension impairs the accessibility of the glycosaminoglycan binding sites and may thus serve as an intrinsic modulator of biological activity.
人 C-C 基序趋化因子 16（CCL16）是一种趋化因子，其特征在于具有未知意义的大可切割 C 末端延伸。关于其组织分布和表达的调节，已有相互矛盾的数据报道，这使得 CCL16 的生物学功能扑朔迷离。在这里，我们报告了一种综合的方法来描述这种趋化因子，包括对其表达特征的重新评估以及对其结构和动力学的生物物理研究。我们的数据表明，CCL16 主要由肝细胞合成，对炎症介质没有明显的反应，并以全长蛋白的形式在血液中循环。虽然 CCL16 的晶体结构证实了存在典型的趋化因子结构域，但分子动力学模拟支持这样的观点，即 C 末端延伸会降低糖胺聚糖结合位点的可及性，因此可能作为生物活性的内在调节剂。
