Proposed mechanism of interaction between GPIbα and the A1 domain of VWF. Proposed mechanism of interaction between GPIbα and the A1 domain of VWF based on the data from Tischer et al¹⁶  and the results of the current manuscript. GPIbα is mostly binding-incompetent when the C-terminal disulfide loop is structured and “attached” to its palm. Destabilization of the C-terminal disulfide loop enables a binding-competent conformation in which GPIbα can interact tightly with the A1 domain of VWF. Protein structure homology modeling of the ligand-binding region of GPIbα and for the A1 domain of VWF was performed using the SWISS-MODEL workspace. The SWISS-MODEL template library (GPIbα SMTL ID:3P72, PDB release 2017-01-26; VWFA1 SMTL ID: 1AUQ, PDB release 1998-10-14) was searched with Blast and HHBlits for evolutionary related structures matching the target sequence.