Immunohematology and Genomics Laboratory, New York Blood Center, New York City, New York, USA.
Laboratoire de Biologie Medicale de Reference en Immunohematologie Moleculaire, Etablissement francais du sang Ile-de-France, Creteil, France.
Transfusion. 2023 Jan;63(1):230-238. doi: 10.1111/trf.17182. Epub 2022 Nov 8.
Scianna (Sc) antigens, seven high and two of low prevalence, are expressed on erythrocyte membrane-associated protein (ERMAP). We investigated SC (ERMAP) in individuals who made antibodies to high prevalence Scianna antigens, and propose a 3D model for ERMAP to precisely localize the residues associated with the known antigens.
Serological testing and DNA sequencing was performed by standard methods. A 3D structural model was built using a multi-template homology approach. Protein structures representing missense variants associated with the loss or gain of an antigen were generated. Residue accessibility and intraprotein interactions were compared with the wild-type protein.
Two new SC alleles, one with c.349C > T (p.Arg117Cys) in a woman from South India with anti-Sc3 in her plasma, and a c.217_219delinsTGT (p.Arg73Cys) in an African-American woman with an antibody to a new high prevalence antigen, termed SCAC, were identified. Six structural templates were used to model ERMAP. 3D analysis showed that residues key for Scianna antigen expression were all exposed at the surface of the extracellular domain. The p.Arg117Cys change was predicted to abolish interactions between residues 93 and 117, with no compensating interactions.
We confirm the extracellular location of Scianna residues responsible for antigen expression which predicts direct accessibility to antibodies. Loss of intraprotein interactions appear to be responsible for a Sc null and production of anti-Sc3 with p.117Cys, SC*01 N.03, and for loss of a high prevalence antigen with p.73Cys, termed SCAC for Sc Arg to Cys. Comparative modeling aids our understanding of new alleles and Scianna antigen expression.
Scianna (Sc) 抗原，七个高流行和两个低流行，表达在红细胞膜相关蛋白 (ERMAP) 上。我们研究了在高流行 Scianna 抗原抗体产生者中的 SC（ERMAP），并提出了一个 3D 模型，以精确定位与已知抗原相关的残基。
通过标准方法进行血清学检测和 DNA 测序。使用多模板同源性方法构建 3D 结构模型。生成与抗原丢失或获得相关的错义变体的蛋白质结构。比较残基的可及性和蛋白质内相互作用与野生型蛋白。
在一位来自印度南部的女性中发现了一种新的 SC 等位基因，其血浆中有抗 Sc3，其 c.349C>T (p.Arg117Cys)；在一位非洲裔美国女性中发现了一种新的高流行抗原抗体，其 c.217_219delinsTGT (p.Arg73Cys)。使用六个结构模板对 ERMAP 进行建模。3D 分析表明，Scianna 抗原表达的关键残基均暴露在细胞外结构域的表面。预测 p.Arg117Cys 改变会破坏残基 93 和 117 之间的相互作用，没有补偿性相互作用。
我们证实了负责抗原表达的 Scianna 残基位于细胞外，这预示着抗体的直接可及性。蛋白质内相互作用的丧失似乎是导致 Sc 缺失和产生抗 Sc3 的原因，该抗体由 p.117Cys 引起，SC*01 N.03，以及由 p.73Cys 引起的高流行抗原缺失，称为 SCAC，即 Sc Arg 到 Cys。比较建模有助于我们理解新的等位基因和 Scianna 抗原的表达。
