Hoover D M, Chertov O, Lubkowski J
Macromolecular Crystallography Laboratory and the Intramural Research Support Program, LMI, SAIC Frederick, NCI at Frederick, National Institutes of Health, Frederick, Maryland 21702, USA.
J Biol Chem. 2001 Oct 19;276(42):39021-6. doi: 10.1074/jbc.M103830200. Epub 2001 Aug 2.
Defensins are a class of small cationic peptides found in higher organisms that serve as both antimicrobial and cell signaling molecules. The exact mechanism of the antimicrobial activity of defensins is not known, but two models have been postulated, one involving pore formation and the other involving nonspecific electrostatic interaction with the bacterial membrane. Here we report the high resolution structures of human beta-defensin-1 (hBD1) in two crystallographic space groups. The structure of a single molecule is very similar to that of human beta-defensin-2 (hBD2), confirming the presence of an N-terminal alpha-helix. However, while the packing of hBD1 is conserved across both space groups, there is no evidence for any larger quaternary structure similar to octameric hBD2. Furthermore, the topology of hBD1 dimers that are formed between monomers in the asymmetric unit is distinct from both hBD2 and other mammalian alpha-defensins. The structures of hBD1 and hBD2 provide a first step toward understanding the structural basis of antimicrobial and chemotactic properties of human beta-defensins.
防御素是一类在高等生物中发现的小阳离子肽，它们既是抗菌分子，也是细胞信号分子。防御素抗菌活性的确切机制尚不清楚，但已提出两种模型，一种涉及孔形成，另一种涉及与细菌膜的非特异性静电相互作用。在此，我们报告了人β-防御素-1（hBD1）在两个晶体学空间群中的高分辨率结构。单个分子的结构与人类β-防御素-2（hBD2）非常相似，证实了N端α-螺旋的存在。然而，虽然hBD1在两个空间群中的堆积是保守的，但没有证据表明存在任何类似于八聚体hBD2的更大四级结构。此外，在不对称单元中单体之间形成的hBD1二聚体的拓扑结构与hBD2和其他哺乳动物α-防御素都不同。hBD1和hBD2的结构为理解人类β-防御素抗菌和趋化特性的结构基础迈出了第一步。
