Crystal Structure of Human ASB9-2 and Substrate-Recognition of CKB
Abstract
Human ankyrin repeat and suppressor of cytokine signaling box protein 9 (hASB9) is a specific substrate-recognition subunit of an elongin C-cullin-SOCS box E3 ubiquitin ligase complex. It recognizes its substrate, brain type creatine kinase (CKB), using the ankyrin repeat domain; and facilitates the polyubiquitination of CKB to mediate proteasomal degradation through the SOCS box domain. HASB9-2 is an isoform of hASB9 that contains one ankyrin repeat domain. In this study, the crystal structure of hASB9-2 is shown at 2.2-Å resolution using molecular replacement. Overall, hASB9-2 forms a slightly curved arch with a characteristic L-shaped cross-section. Amino acid substitution analysis based on docking experiments revealed that His103 and Phe107 in hASB9-2 are essential for binding to CKB. Analysis of truncation mutants demonstrated that the first six ankyrin repeats along with the N-terminal region of hASB9-2 contribute to the interaction with CKB.
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Structural data for ASB9 reveal juxtaposed hydrophobic cavities in the substrate-binding domain.
“structural data for ASB9 reveal juxtaposed hydrophobic cavities in the substrate-binding domain”
From Targeted protein degradation: expanding the toolbox (2019) · cites this paper as [106]
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Targeted protein degradation: expanding the toolbox
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- Authors
- Fei, X., Gu, X., Fan, S., Yang, Z., Li, F., Zhang, C., Gong, W., Mao, Y., & Ji, C.
- Affiliations
- Fudan University (CN)
- Chinese Academy of Sciences (CN)
- Corresponding author
- Ji, Chaoneng
- Venue
- The Protein Journal
- Published
- 2012-03-15
- Volume
- 31
- Issue
- 4
- Pages
- 275-284
- ISSN
- 1572-3887 (ISSN-L)
- 1875-8355
- OpenAlex
- W2031468303
- Cited by
- 12
- References
- 29
- Citations by year
- 2024: 1 · 2023: 1 · 2019: 2 · 2018: 2 · 2016: 3 · 2015: 1 · 2013: 2
- FWCI
- 0.39
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Protein Journal (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Physical Sciences › Materials Science › Materials Chemistry › Enzyme Structure and Function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Keywords
- ankyrin repeat domain, brain-type creatine kinase, substrate recognition, polyubiquitination, proteasomal degradation, protein-protein interaction, crystal structure, truncation mutants
- MeSH terms
- Amino Acid Sequence, Binding Sites, Humans, Kinetics, Models, Molecular, Molecular Sequence Data, Protein Binding, Substrate Specificity, Sequence Alignment, Ankyrin Repeat, Crystallography, X-Ray, Suppressor of Cytokine Signaling Proteins, Creatine Kinase, BB Form
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