DC Field | Value | Language |
---|---|---|
dc.contributor.author | Kim, Hyojin | ko |
dc.contributor.author | Fu, Yaoyao | ko |
dc.contributor.author | Hong, Ho Jeong | ko |
dc.contributor.author | Lee, Seong-Gyu | ko |
dc.contributor.author | Lee, Dong Sun | ko |
dc.contributor.author | Kim, Ho Min | ko |
dc.date.accessioned | 2022-08-08T01:00:12Z | - |
dc.date.available | 2022-08-08T01:00:12Z | - |
dc.date.created | 2022-08-07 | - |
dc.date.created | 2022-08-07 | - |
dc.date.created | 2022-08-07 | - |
dc.date.issued | 2022-07 | - |
dc.identifier.citation | NATURE COMMUNICATIONS, v.13, no.1 | - |
dc.identifier.issn | 2041-1723 | - |
dc.identifier.uri | http://hdl.handle.net/10203/297850 | - |
dc.description.abstract | Insulin-like growth factors (IGFs) have pleiotropic roles in embryonic and postnatal growth and differentiation. Most serum IGFs are bound in a ternary complex with IGF-binding protein 3 (IGFBP3) and acid-labile subunit (ALS), extending the serum half-life of IGFs and regulating their availability. Here, we report cryo-EM structure of the human IGF1/IGFBP3/ALS ternary complex, revealing the detailed architecture of a parachute-like ternary complex and crucial determinants for their sequential and specific assembly. In vitro biochemical studies show that proteolysis at the central linker domain of IGFBP3 induces release of its C-terminal domain rather than IGF1 release from the ternary complex, yielding an intermediate complex that enhances IGF1 bioavailability. Our results provide mechanistic insight into IGF/IGFBP3/ALS ternary complex assembly and its disassembly upon proteolysis for IGF bioavailability, suggesting a structural basis for human diseases associated with IGF1 and IGFALS gene mutations such as complete ALS deficiency (ACLSD) and IGF1 deficiency. | - |
dc.language | English | - |
dc.publisher | NATURE PORTFOLIO | - |
dc.title | Structural basis for assembly and disassembly of the IGF/IGFBP/ALS ternary complex | - |
dc.type | Article | - |
dc.identifier.wosid | 000834693800008 | - |
dc.identifier.scopusid | 2-s2.0-85135139909 | - |
dc.type.rims | ART | - |
dc.citation.volume | 13 | - |
dc.citation.issue | 1 | - |
dc.citation.publicationname | NATURE COMMUNICATIONS | - |
dc.identifier.doi | 10.1038/s41467-022-32214-2 | - |
dc.contributor.localauthor | Kim, Ho Min | - |
dc.contributor.nonIdAuthor | Fu, Yaoyao | - |
dc.contributor.nonIdAuthor | Hong, Ho Jeong | - |
dc.contributor.nonIdAuthor | Lee, Seong-Gyu | - |
dc.contributor.nonIdAuthor | Lee, Dong Sun | - |
dc.description.isOpenAccess | N | - |
dc.type.journalArticle | Article | - |
dc.subject.keywordPlus | ACID-LABILE SUBUNIT | - |
dc.subject.keywordPlus | GROWTH-FACTOR-I | - |
dc.subject.keywordPlus | FACTOR (IGF)-BINDING PROTEIN-3 | - |
dc.subject.keywordPlus | IGF-BINDING PROTEIN-3 | - |
dc.subject.keywordPlus | SHORT STATURE | - |
dc.subject.keywordPlus | HIGH-AFFINITY | - |
dc.subject.keywordPlus | SERUM | - |
dc.subject.keywordPlus | GLYCOSYLATION | - |
dc.subject.keywordPlus | PROTEOLYSIS | - |
dc.subject.keywordPlus | MECHANISMS | - |
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