Istitute of Biostructures and Bioimaging, CNR, Naples, Italy.
FEBS Lett. 2010 Mar 19;584(6):1091-6. doi: 10.1016/j.febslet.2010.02.044. Epub 2010 Feb 20.
Heparin Binding Hemagglutinin A (HBHA) is hitherto the sole virulence factor associated with tuberculosis dissemination from the lungs, the site of primary infection, to epithelial cells. We have previously reported the solution structure of HBHA, a dimeric and elongated molecule. Since oligomerisation of HBHA is associated with its ability to induce bacterial agglutination, we investigated this process using experimental and modelling techniques. We here identified a short segment of HBHA whose presence is mandatory for the stability of folded conformation, whose denaturation is a reversible two-state process. Our data suggest that agglutination-driven cell-cell interactions do not occur via association of HBHA monomers, nor via association of HBHA dimers and open the scenario to a possible trans-dimerisation process.
肝素结合血凝素 A（HBHA）是迄今为止唯一与结核分枝杆菌从肺部原发感染部位向上皮细胞传播相关的毒力因子。我们之前已经报道了 HBHA 的溶液结构，它是一个二聚体和长形分子。由于 HBHA 的寡聚化与其诱导细菌聚集的能力相关，我们使用实验和建模技术研究了这个过程。我们在这里确定了 HBHA 的一个短片段，其存在对于折叠构象的稳定性是必需的，其变性是一个可逆的两态过程。我们的数据表明，聚集驱动的细胞-细胞相互作用不是通过 HBHA 单体的缔合，也不是通过 HBHA 二聚体的缔合发生的，这为可能的反式二聚化过程开辟了可能性。
