Rydengård Victoria, Olsson Anna-Karin, Mörgelin Matthias, Schmidtchen Artur
Section of Dermatology and Venereology, Lund University, Sweden.
FEBS J. 2007 Jan;274(2):377-89. doi: 10.1111/j.1742-4658.2006.05586.x.
Histidine-rich glycoprotein (HRGP), an abundant heparin-binding protein found in plasma and thrombocytes, exerts antibacterial effects against Gram-positive bacteria (Enterococcus faecalis and Staphylococcus aureus) and Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa). Fluorescence studies and electron microscopy to assess membrane permeation showed that HRGP induces lysis of E. faecalisbacteria in the presence of Zn2+ or at low pH. Heparin blocked binding of the protein to E. faecalis and abolished antibacterial activity. Furthermore, truncated HRGP, devoid of the heparin-binding and histidine-rich domain, was not antibacterial. It has previously been shown that peptides containing consensus heparin-binding sequences (Cardin and Weintraub motifs) are antibacterial. Thus, the peptide (GHHPH)4, derived from the histidine-rich region of HRGP and containing such a heparin-binding motif, was antibacterial for E. faecalis in the presence of Zn2+ or at low pH. The results show a previously undisclosed antibacterial activity of HRGP and suggest that the histidine-rich and heparin-binding domain of HRGP mediates the antibacterial activity of the protein.
富含组氨酸的糖蛋白（HRGP）是一种在血浆和血小板中发现的丰富的肝素结合蛋白，对革兰氏阳性菌（粪肠球菌和金黄色葡萄球菌）和革兰氏阴性菌（大肠杆菌和铜绿假单胞菌）具有抗菌作用。用于评估膜渗透的荧光研究和电子显微镜显示，HRGP在Zn2+存在或低pH条件下可诱导粪肠球菌裂解。肝素可阻断该蛋白与粪肠球菌的结合并消除抗菌活性。此外，缺乏肝素结合和富含组氨酸结构域的截短型HRGP没有抗菌作用。此前已表明，含有共有肝素结合序列（卡丹和温特劳布基序）的肽具有抗菌作用。因此，源自HRGP富含组氨酸区域且含有此类肝素结合基序的肽（GHHPH）4在Zn2+存在或低pH条件下对粪肠球菌具有抗菌作用。结果显示了HRGP此前未被揭示的抗菌活性，并表明HRGP富含组氨酸和肝素结合结构域介导了该蛋白的抗菌活性。
