Fig. 2: SEL1L disease variants disrupt OS9-SEL1L and SEL1L-HRD1 interactions.
From: Structural basis and pathological implications of the dimeric OS9-SEL1L-HRD1 ERAD Core Complex
a, b View from ER lumen (a) or the side (b) with space-filling model for OS9-SEL1L complex. Red asterisk indicates the opening formed by SEL1L-OS9 in substrate-binding crab “claw”-like configuration. The position of SEL1L-G585 residue (purple sphere) shown in (b). 4β, the four β-sheet domain of OS9. MRH, mannose-6-phosphate receptor homology domain of OS9. APH, amphipathic helix of SEL1L. c Interface of OS9-SEL1L interaction with SEL1L-G585 residue shown as a purple sphere, with the cryo-EM map shown as mesh. d Close-up view with space-filling model for SEL1L-HRD1 showing the SEL1L-HRD1 interaction interface, with SEL1L-S658 residue shown as a red sphere. APH, amphipathic helix of SEL1L. e Interface of SEL1L-HRD1 interaction with SEL1L-S658 residue shown as a red sphere, with the cryo-EM map shown as mesh. f Immunoprecipitation of FLAG-agarose in SEL1L-/- HEK293T cells transfected with indicated SEL1L variants to examine their interaction with HRD1, OS9 and E2 UBE2J1, with quantitation of interaction levels with SEL1L shown on the right (three independent repeats. p value in HRD1: G585D p = 0.0101, S658P p < 0.0001, G585D;S658P p < 0.0001; p value in OS9: G585D p < 0.0001, S658P p > 0.9999, G585D;S658P p < 0.0001; p value in UBE2J1, G585D p > 0.9999, S658P p = 0.9935, G585D;S658P p = 0.4808). Values, mean ± SEM. n.s., not significant; *p < 0.05 and ****p < 0.0001 by one-way ANOVA test with comparison to WT. Source data are provided as a Source Data file.
