Fig. 1

Structure of the AF6 RA1 domain complex with activated RAS. a The RAS effector AF6 is commonly fused to the epigenetic regulator MLL following a translocation that initiates leukemogenesis. The detected fusion protein connects the N-terminal 1395 residues of MLL to residues 36–1651 of AF6. b Size exclusion chromatography of purified AF6 RA1 domain (residues 37–136) presents two peaks, corresponding to monomer and dimer fractions, at several concentrations. c Ribbons diagram and surface overlay for crystal structure of the AF6 RA1 domain (blue) complexed with RAS (red) bound to GMPPNP (yellow). Statistics in Supplementary Fig. 2c. d Ribbons diagram shows the binding interface between AF6 RA1 domain (blue) and RAS-GMPPNP (red–yellow). Contact residues are labeled and displayed as sticks. e Structural alignment of AF6 RA1 domain (blue) complexed with RAS-GMPPNP (gray) and RASSF5 RA domain (orange) bound to RAS-GMPPNP (PDB 3DDC). RASSF5 is the only known RAS effector with an αN helix that contacts the switch II region of RAS. f RASSF5 contacts the RAS switch II region via an α-helix located N-terminal to the β1-strand of the RA domain (top, from PDB 3DDC). Predictions of secondary structure upstream of β1 from the AF6 RA1 domain suggest the presence of an analogous helix (bottom, dashed). H = α-helix, S = β-strand (JPRED)