![Figure 2. The D′ domain interfaces primarily with the FVIII C1 domain. 3D reconstruction of the murine [D′D3]2-FVIII ternary complex (determined from 962 projections) reveals the D′ density (suggested by the yellow shell) extending from the [D3]2 core and enmeshed with the region corresponding to the FVIII C domains. The structure of FVIII14 (Protein Data Bank: 2R7E) fits the EM density in a unique orientation (A1, olive; A2, green; A3, cyan; C1, blue; C2, purple). The suboptimal agreement between the EM envelope and the position of the C domains suggests that they likely undergo conformational changes upon interaction with VWF D′. Modeling of the VWF D′ domain (Protein Data Bank: 2MHP, red) within the corresponding EM density suggests that it interacts primarily with the FVIII C1 domain, although more limited interactions are possible with C2 and A3. The N- and C-termini of the VWF D′ domain are represented by spheres and indicated by black arrows.](https://ash.silverchair-cdn.com/ash/content_public/journal/blood/126/8/10.1182_blood-2015-04-641696/4/939f2.jpeg?Expires=1725247092&Signature=1SO0P4DQz2GFtewgSkN98hlL4Tup5mDfgwcGeC1FPEhPStoQy0wULsWYDb9gbtKJx3~Ft3vpLxrgksjj9R84PrbcCA1PTIo4X-1XfQp-U56ws6UUJqLyujNsxCdGIzHOKyaOUvRNfJZ5iY2AQUmBjQmfQb9H2MKUxHoxW2kqGwBqBUcQWkgclwnLCPlxWKj~GGHnalOY4fNurHgFrxK1jmPqX3GkYHCpE6e~gfZgDlFihepUGMKRowpd4ZRLmR2XgUkv0o~3dI66Cg9OJCEr9mfeAKKSyw8SFqNaf~kXJGjduGn1qb1IOmyw7~eUHUtQis4Rme5HxOAxcrlF43-3iA__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA)
The D′ domain interfaces primarily with the FVIII C1 domain. 3D reconstruction of the murine [D′D3]2-FVIII ternary complex (determined from 962 projections) reveals the D′ density (suggested by the yellow shell) extending from the [D3]2 core and enmeshed with the region corresponding to the FVIII C domains. The structure of FVIII14 (Protein Data Bank: 2R7E) fits the EM density in a unique orientation (A1, olive; A2, green; A3, cyan; C1, blue; C2, purple). The suboptimal agreement between the EM envelope and the position of the C domains suggests that they likely undergo conformational changes upon interaction with VWF D′. Modeling of the VWF D′ domain (Protein Data Bank: 2MHP, red) within the corresponding EM density suggests that it interacts primarily with the FVIII C1 domain, although more limited interactions are possible with C2 and A3. The N- and C-termini of the VWF D′ domain are represented by spheres and indicated by black arrows.
