Proposed intramolecular chaperone function of the VWFpp.

The propeptide of VWF functions as an intramolecular chaperone. The contiguous molecule folds VWF into the correct orientation necessary for proper intermolecular bridging by the cysteines in the adjacent dimers (panel A). The VWFpp role may be to tether the molecules together, allowing the cysteines to interact. The Tyr87Ser VWF defect and possibly other type IIC VWD defects cause the region to assume an incorrect configuration (panel B), and thus prevent the proper contact between adjacent dimers that results in a loss of N-terminal multimerization.