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-Structure paper
| タイトル | Structure of apolipoprotein B100 bound to the low-density lipoprotein receptor. |
|---|---|
| ジャーナル・号・ページ | Nature, Vol. 638, Issue 8051, Page 829-835, Year 2025 |
| 掲載日 | 2024年12月11日 |
著者 | Mart Reimund / Altaira D Dearborn / Giorgio Graziano / Haotian Lei / Anthony M Ciancone / Ashish Kumar / Ronald Holewinski / Edward B Neufeld / Francis J O'Reilly / Alan T Remaley / Joseph Marcotrigiano / ![]() |
| PubMed 要旨 | Apolipoprotein B100 (apoB100) is a structural component of low-density lipoprotein (LDL) and a ligand for the LDL receptor (LDLR). Mutations in apoB100 or in LDLR cause familial ...Apolipoprotein B100 (apoB100) is a structural component of low-density lipoprotein (LDL) and a ligand for the LDL receptor (LDLR). Mutations in apoB100 or in LDLR cause familial hypercholesterolaemia, an autosomal dominant disease that is characterized by a marked increase in LDL cholesterol (LDL-C) and a higher risk of cardiovascular disease. The structure of apoB100 on LDL and its interaction with LDLR are poorly understood. Here we present the cryo-electron microscopy structures of apoB100 on LDL bound to the LDLR and a nanobody complex, which can form a C-symmetric, higher-order complex. Using local refinement, we determined high-resolution structures of the interfaces between apoB100 and LDLR. One binding interface is formed between several small-ligand-binding modules of LDLR and a series of basic patches that are scattered along a β-belt formed by apoB100, encircling LDL. The other binding interface is formed between the β-propeller domain of LDLR and the N-terminal domain of apoB100. Our results reveal how both interfaces are involved in LDL dimer formation, and how LDLR cycles between LDL- and self-bound conformations. In addition, known mutations in either apoB100 or LDLR, associated with high levels of LDL-C, are located at the LDL-LDLR interface. |
リンク | Nature / PubMed:39663455 |
| 手法 | EM (単粒子) |
| 解像度 | 3.73 - 8.6 Å |
| 構造データ | ![]() EMDB-44442: Dimeric form of LDL, LDL receptor and Legobody EMDB-44443, PDB-9bd1: EMDB-44446, PDB-9bd8: EMDB-44450, PDB-9bde: EMDB-44469, PDB-9bdt: EMDB-45787, PDB-9coo: |
| 化合物 | ![]() ChemComp-NAG: ![]() ChemComp-CA: |
| 由来 |
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キーワード | LIPID TRANSPORT / Apolipoprotien B 100 / alpha/beta 1 region / LDL / Low density lipoprotein / LDL receptor / Apolipoprotein B 100 / ApoB100 / LDLreceptor |
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