title: Structural insights into the interaction of human p97 N-terminal domain and SHP motif in Derlin-1 rhomboid pseudoprotease.
abstract: The interaction of the rhomboid pseudoprotease Derlin-1 and p97 is crucial for the retrotranslocation of polyubiquitinated substrates in the endoplasmic reticulum-associated degradation pathway. We report a 2.25 Å resolution structure of the p97 N-terminal domain (p97N) in complex with the Derlin-1 SHP motif. Remarkably, the SHP motif adopts a short, antiparallel β-strand that interacts with the β-sheet of p97N-a site distinct from that to which most p97 adaptor proteins bind. Mutational and biochemical analyses contributed to defining the specific interaction, demonstrating the importance of a highly conserved binding pocket on p97N and a signature motif on SHP. Our findings may also provide insights into the interactions between other SHP-containing proteins and p97N.
authors.affiliation: School of Life Science, Gwangju Institute of Science and Technology (GIST), Korea.|Steitz Center for Structural Biology, Gwangju Institute of Science and Technology (GIST), Korea.
authors.forename: Jia Jia
authors.initials: JJ
authors.lastname: Lim
authors.affiliation: School of Life Science, Gwangju Institute of Science and Technology (GIST), Korea.|Steitz Center for Structural Biology, Gwangju Institute of Science and Technology (GIST), Korea.
authors.forename: Youngjin
authors.initials: Y
authors.lastname: Lee
authors.affiliation: School of Life Science, Gwangju Institute of Science and Technology (GIST), Korea.
authors.forename: So Young
authors.initials: SY
authors.lastname: Yoon
authors.affiliation: School of Life Science, Gwangju Institute of Science and Technology (GIST), Korea.|Steitz Center for Structural Biology, Gwangju Institute of Science and Technology (GIST), Korea.
authors.forename: Tue Tu
authors.initials: TT
authors.lastname: Ly
authors.affiliation: School of Life Science, Gwangju Institute of Science and Technology (GIST), Korea.|Steitz Center for Structural Biology, Gwangju Institute of Science and Technology (GIST), Korea.
authors.forename: Jung Youn
authors.initials: JY
authors.lastname: Kang
authors.affiliation: School of Life Science, Gwangju Institute of Science and Technology (GIST), Korea.|Steitz Center for Structural Biology, Gwangju Institute of Science and Technology (GIST), Korea.
authors.forename: Hyung-Seop
authors.initials: HS
authors.lastname: Youn
authors.affiliation: School of Life Science, Gwangju Institute of Science and Technology (GIST), Korea.|Steitz Center for Structural Biology, Gwangju Institute of Science and Technology (GIST), Korea.
authors.forename: Jun Yop
authors.initials: JY
authors.lastname: An
authors.affiliation: School of Life Science, Gwangju Institute of Science and Technology (GIST), Korea.|Steitz Center for Structural Biology, Gwangju Institute of Science and Technology (GIST), Korea.
authors.forename: Jung-Gyu
authors.initials: JG
authors.lastname: Lee
authors.affiliation: School of Life Science, Gwangju Institute of Science and Technology (GIST), Korea.|Steitz Center for Structural Biology, Gwangju Institute of Science and Technology (GIST), Korea.
authors.forename: Kyoung Ryoung
authors.initials: KR
authors.lastname: Park
authors.affiliation: School of Life Science, Gwangju Institute of Science and Technology (GIST), Korea.|Steitz Center for Structural Biology, Gwangju Institute of Science and Technology (GIST), Korea.
authors.forename: Tae Gyun
authors.initials: TG
authors.lastname: Kim
authors.affiliation: Department of Chemistry, College of Natural Sciences, Soongsil University, Seoul, Korea.
authors.forename: Jin Kuk
authors.initials: JK
authors.lastname: Yang
authors.affiliation: School of Life Science, Gwangju Institute of Science and Technology (GIST), Korea.
authors.forename: Youngsoo
authors.initials: Y
authors.lastname: Jun
authors.affiliation: School of Life Science, Gwangju Institute of Science and Technology (GIST), Korea.|Steitz Center for Structural Biology, Gwangju Institute of Science and Technology (GIST), Korea.|Department of Chemistry, Gwangju Institute of Science and Technology (GIST), Korea.
authors.forename: Soo Hyun
authors.initials: SH
authors.lastname: Eom
mesh_terms: D000251:Adenosine Triphosphatases / Q000737:chemistry* / Q000378:metabolism*; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001059:Apoproteins / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites; D017124:Conserved Sequence; D060746:Endoplasmic Reticulum-Associated Degradation; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry* / Q000378:metabolism*; D009687:Nuclear Proteins / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding; D000072417:Protein Domains
chemical_list: D001059:Apoproteins; C487709:DERL1 protein, human; D008565:Membrane Proteins; D009687:Nuclear Proteins; D000251:Adenosine Triphosphatases; C404942:p97 ATPase
keywords: Derlin-1; SHP motif; crystal structure; endoplasmic reticulum-associated degradation; p97