Structure of the human C9orf72-SMCR8 complex reveals a multivalent protein interaction architecture
Fig 2
Structure of the C9orf72-SMCR8N-C complex.
(A) Overview of the cryo-EM map and structure of the C9orf72-SMCR8N-C complex in 2 orientations. C9orf72 (yellow orange) and SMCR8 (salmon pink) are shown as cartoons, and the interfaces between these proteins are boxed and shown in B, C, and D. Dashed lines indicate the 2 separate structural modules of both proteins. (B) Interaction interface 1 between the uDenn domains of C9orf72 (yellow orange) and SMCR8 (salmon pink). The β-sheet extension occurring due to the interaction of C9orf72 and SMCR8 is displayed (left). The interacting residues contributing to the formation of the hydrophobic core are labeled and displayed as sticks (right). (C) Region of interaction interface 2 between the cDenn domains of C9orf72 (yellow orange) and SMCR8 (salmon pink). The interacting residues are labeled and displayed as sticks. (D) Region of interaction interface 2 between the cDenn domain of C9orf72 (yellow orange) and the bridging helix of SMCR8 (salmon pink). The interacting residues are labeled and displayed as sticks. The corresponding cryo-EM map densities at the interaction interfaces are shown in S6 Fig. cDenn, central Denn; cryo-EM, cryo-electron microscopy; dDenn, downstream Denn; Denn, differently expressed in normal and neoplastic cells; uDenn, upstream Denn.