Center for Infectious and Inflammatory Diseases, Institute of Biosciences and Technology, Texas A & M University Health Science Center, Houston, Texas 77030, USA.
J Biol Chem. 2011 Jul 22;286(29):25963-72. doi: 10.1074/jbc.M110.217414. Epub 2011 May 3.
Clumping factor B (ClfB) from Staphylococcus aureus is a bifunctional protein that binds to human cytokeratin 10 (K10) and fibrinogen (Fg). ClfB has been implicated in S. aureus colonization of nasal epithelium and is therefore a key virulence factor. People colonized with S. aureus are at an increased risk for invasive staphylococcal disease. In this study, we have determined the crystal structures of the ligand-binding region of ClfB in an apo-form and in complex with human K10 and Fg α-chain-derived peptides, respectively. We have determined the structures of MSCRAMM binding to two ligands with different sequences in the same site showing the versatile nature of the ligand recognition mode of microbial surface components recognizing adhesive matrix molecules. Both ligands bind ClfB by parallel β-sheet complementation as observed for the clumping factor A·γ-chain peptide complex. The β-sheet complementation is shorter in the ClfB·Fg α-chain peptide complex. The structures show that several residues in ClfB are important for binding to both ligands, whereas others only make contact with one of the ligands. A common motif GSSGXG found in both ligands is part of the ClfB-binding site. This motif is found in many human proteins thus raising the possibility that ClfB recognizes additional ligands.
金黄色葡萄球菌的凝聚因子 B（ClfB）是一种具有双重功能的蛋白质，可与人细胞角蛋白 10（K10）和纤维蛋白原（Fg）结合。ClfB 与金黄色葡萄球菌在鼻腔上皮的定植有关，因此是一个关键的毒力因子。定植有金黄色葡萄球菌的人患侵袭性葡萄球菌病的风险增加。在这项研究中，我们分别确定了 ClfB 的配体结合区在apo 形式和与人类 K10 和 Fg α-链衍生肽复合物中的晶体结构。我们已经确定了在同一部位与两种具有不同序列的配体结合的结构，显示了微生物表面成分识别粘附基质分子的配体识别模式的多功能性质。两种配体均通过平行的β-折叠互补与 ClfB 结合，如凝聚因子 A·γ-链肽复合物中观察到的那样。β-折叠互补在 ClfB·Fg α-链肽复合物中较短。结构表明，ClfB 中的几个残基对于与两种配体的结合都很重要，而其他残基仅与其中一种配体接触。在两种配体中都发现的一个常见基序 GSSGXG 是 ClfB 结合位点的一部分。该基序存在于许多人类蛋白中，因此有可能 ClfB 识别其他配体。
