Scanlon M J, Morley S D, Jackson D E, Price M R, Tendler S J
Department of Pharmaceutical Sciences, University of Nottingham, U.K.
Biochem J. 1992 May 15;284 ( Pt 1)(Pt 1):137-44. doi: 10.1042/bj2840137.
Human polymorphic epithelial mucins (PEM) are complex glycoproteins that are associated with breast and ovarian carcinomas. The PEM core protein consists of variable numbers of a tandem repeat sequence which contains a short antigenic hydrophilic region (Pro1-Asp-Thr-Arg-Pro-Ala-Pro7). High-field n.m.r. studies undertaken on antigenic 20- and 11-amino acid fragments of the PEM core protein in dimethyl sulphoxide have identified a type-I beta-turn to be present in the region Pro1-Asp-Thr-Arg4. This region includes and overlaps the identified type-I (Asp2-Thr-Arg4) and type-II (Arg4-Pro-Ala6) epitopes of anti-PEM monoclonal antibodies. The studies indicate that the beta-turn is stabilized by the presence of a salt-bridge interaction between Asp-2 and Arg-4. In order to probe the conformations accessible to the PEM peptides a computational study was undertaken independently on the peptide Pro-Asp-Thr-Arg-Pro using a modified Metropolis Monte Carlo algorithm. This study identified the n.m.r.-observed salt-bridge type-I beta-turn as the major low-energy conformer. These results suggest that this structural motif may be involved in the immune recognition of PEM.
人类多态性上皮粘蛋白（PEM）是与乳腺癌和卵巢癌相关的复合糖蛋白。PEM核心蛋白由可变数量的串联重复序列组成，该序列包含一个短的抗原性亲水区域（Pro1-Asp-Thr-Arg-Pro-Ala-Pro7）。在二甲基亚砜中对PEM核心蛋白的抗原性20氨基酸和11氨基酸片段进行的高场核磁共振研究表明，在Pro1-Asp-Thr-Arg4区域存在I型β-转角。该区域包括并与抗PEM单克隆抗体已确定的I型（Asp2-Thr-Arg4）和II型（Arg4-Pro-Ala6）表位重叠。研究表明，β-转角通过Asp-2和Arg-4之间的盐桥相互作用而稳定。为了探究PEM肽可及的构象，使用改进的Metropolis蒙特卡罗算法对肽Pro-Asp-Thr-Arg-Pro进行了独立的计算研究。该研究确定核磁共振观察到的盐桥I型β-转角是主要的低能构象体。这些结果表明，这种结构基序可能参与了PEM的免疫识别。
