Maritan Martina, Cozzi Roberta, Lo Surdo Paola, Veggi Daniele, Bottomley Matthew James, Malito Enrico
GSK Vaccines, Via Fiorentina 1, 53100 Siena, Italy.
Acta Crystallogr F Struct Biol Commun. 2017 Jun 1;73(Pt 6):305-314. doi: 10.1107/S2053230X17006021. Epub 2017 May 11.
Neisserial heparin-binding antigen (NHBA) is a surface-exposed lipoprotein from Neisseria meningitidis and is a component of the meningococcus B vaccine Bexsero. As part of a study to characterize the three-dimensional structure of NHBA and the molecular basis of the human immune response to Bexsero, the crystal structures of two fragment antigen-binding domains (Fabs) isolated from human monoclonal antibodies targeting NHBA were determined. Through a high-resolution analysis of the organization and the amino-acid composition of the CDRs, these structures provide broad insights into the NHBA epitopes recognized by the human immune system. As expected, these Fabs also show remarkable structural conservation, as shown by a structural comparison of 15 structures of apo Fab 10C3 which were obtained from crystals grown in different crystallization conditions and were solved while searching for a complex with a bound NHBA fragment or epitope peptide. This study also provides indirect evidence for the intrinsically disordered nature of two N-terminal regions of NHBA.
奈瑟菌肝素结合抗原（NHBA）是脑膜炎奈瑟菌的一种表面暴露脂蛋白，是B群脑膜炎球菌疫苗Bexsero的一个成分。作为一项表征NHBA三维结构以及人类对Bexsero免疫反应分子基础研究的一部分，测定了从靶向NHBA的人单克隆抗体中分离出的两个片段抗原结合域（Fab）的晶体结构。通过对互补决定区（CDR）的组织和氨基酸组成进行高分辨率分析，这些结构为人类免疫系统识别的NHBA表位提供了广泛的见解。正如预期的那样，这些Fab也显示出显著的结构保守性，从在不同结晶条件下生长并在寻找与结合的NHBA片段或表位肽的复合物时解析得到的15个脱辅基Fab 10C3结构的结构比较中可以看出。这项研究还为NHBA两个N端区域的内在无序性质提供了间接证据。
