Two new Scianna variants causing loss of high prevalence antigens: ERMAP model and 3D analysis of the antigens.
Transfusion
; 63(1): 230-238, 2023 01.
Article
em En
| MEDLINE
| ID: mdl-36349441
ABSTRACT
BACKGROUND:
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.METHODS:
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.RESULTS:
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.CONCLUSION:
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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Antígenos de Grupos Sanguíneos
Tipo de estudo:
Prevalence_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Female
/
Humans
País/Região como assunto:
Asia
Idioma:
En
Revista:
Transfusion
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Estados Unidos