Background
Vel is a clinically relevant blood group antigen known to be carried by the small integral membrane protein 1 (SMIM1). The presentation of the Vel epitope requires inter-molecular disulfide bonds and a functional GXXXG-motif, which reportedly supports the dimerization of membrane proteins. The exact structure of the Vel epitope, however, remains elusive so far.
Methods
A putative Vel epitope was modelled using artificial intelligence supported structure prediction of dimers of SMIM1 and SMIM1 variants.
Results
Two conditions were considered necessary for a model of the Vel epitope to be acceptable: firstly, the formation of an inter-molecular disulfide bond, and secondly, the correct orientation of the GXXXG-motif. Modelling a Vel dimer without constraints fulfilled neither the first nor the second condition. After an iterative process of adding other structural motifs and linkers, a model was obtained that fulfilled both conditions (Fig 1).
Conclusion
The dimerization of SMIM1 puts a certain apparent stress on the structure, which probably requires the disulfide bond to remain stable. This could explain why the disulfide bond is crucial for the presentation of the Vel antigen and anti-Vel antibodies seem to be mostly conformation dependent. The modelled Vel epitope still needs experimental validation.
Offenlegung Interessenkonflikt:
Angestellter bei imusyn GmbH & Co. KG
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