title: Crystal structure of SEL1L: Insight into the roles of SLR motifs in ERAD pathway.
abstract: Terminally misfolded proteins are selectively recognized and cleared by the endoplasmic reticulum-associated degradation (ERAD) pathway. SEL1L, a component of the ERAD machinery, plays an important role in selecting and transporting ERAD substrates for degradation. We have determined the crystal structure of the mouse SEL1L central domain comprising five Sel1-Like Repeats (SLR motifs 5 to 9; hereafter called SEL1L(cent)). Strikingly, SEL1L(cent) forms a homodimer with two-fold symmetry in a head-to-tail manner. Particularly, the SLR motif 9 plays an important role in dimer formation by adopting a domain-swapped structure and providing an extensive dimeric interface. We identified that the full-length SEL1L forms a self-oligomer through the SEL1L(cent) domain in mammalian cells. Furthermore, we discovered that the SLR-C, comprising SLR motifs 10 and 11, of SEL1L directly interacts with the N-terminus luminal loops of HRD1. Therefore, we propose that certain SLR motifs of SEL1L play a unique role in membrane bound ERAD machinery.
authors.affiliation: Department of Biological Sciences, School of Life Sciences, Ulsan National Institute of Science and Technology, 50 UNIST-gil, Ulsan 44919, Republic of Korea.
authors.forename: Hanbin
authors.initials: H
authors.lastname: Jeong
authors.affiliation: Department of Biological Sciences, School of Life Sciences, Ulsan National Institute of Science and Technology, 50 UNIST-gil, Ulsan 44919, Republic of Korea.
authors.forename: Hyo Jung
authors.initials: HJ
authors.lastname: Sim
authors.affiliation: Department of Biological Sciences, School of Life Sciences, Ulsan National Institute of Science and Technology, 50 UNIST-gil, Ulsan 44919, Republic of Korea.
authors.forename: Eun Kyung
authors.initials: EK
authors.lastname: Song
authors.affiliation: Department of Biological Sciences, School of Life Sciences, Ulsan National Institute of Science and Technology, 50 UNIST-gil, Ulsan 44919, Republic of Korea.
authors.forename: Hakbong
authors.initials: H
authors.lastname: Lee
authors.affiliation: Pohang Accelerator Laboratory, Pohang University of Science and Technology, Pohang, Kyungbuk 37673, Korea.
authors.forename: Sung Chul
authors.initials: SC
authors.lastname: Ha
authors.affiliation: School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 61005, Korea.
authors.forename: Youngsoo
authors.initials: Y
authors.lastname: Jun
authors.affiliation: Department of Biological Sciences, School of Life Sciences, Ulsan National Institute of Science and Technology, 50 UNIST-gil, Ulsan 44919, Republic of Korea.
authors.forename: Tae Joo
authors.initials: TJ
authors.lastname: Park
authors.affiliation: Department of Biological Sciences, School of Life Sciences, Ulsan National Institute of Science and Technology, 50 UNIST-gil, Ulsan 44919, Republic of Korea.
authors.forename: Changwook
authors.initials: C
authors.lastname: Lee
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D018360:Crystallography, X-Ray; D060746:Endoplasmic Reticulum-Associated Degradation; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*; D020449:Repetitive Sequences, Amino Acid
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; C492169:Sel1h protein, mouse