|
|
| Line 1: |
Line 1: |
| [[Image:3bps.jpg|left|200px]] | | {{Seed}} |
| | [[Image:3bps.png|left|200px]] |
|
| |
|
| <!-- | | <!-- |
| Line 9: |
Line 10: |
| {{STRUCTURE_3bps| PDB=3bps | SCENE= }} | | {{STRUCTURE_3bps| PDB=3bps | SCENE= }} |
|
| |
|
| '''PCSK9:EGF-A complex'''
| | ===PCSK9:EGF-A complex=== |
|
| |
|
|
| |
|
| ==Overview==
| | <!-- |
| Proprotein convertase subtilisin/kexin type 9 (PCSK9) posttranslationally regulates hepatic low-density lipoprotein receptors (LDLRs) by binding to LDLRs on the cell surface, leading to their degradation. The binding site of PCSK9 has been localized to the epidermal growth factor-like repeat A (EGF-A) domain of the LDLR. Here, we describe the crystal structure of a complex between PCSK9 and the EGF-A domain of the LDLR. The binding site for the LDLR EGF-A domain resides on the surface of PCSK9's subtilisin-like catalytic domain containing Asp-374, a residue for which a gain-of-function mutation (Asp-374-Tyr) increases the affinity of PCSK9 toward LDLR and increases plasma LDL-cholesterol (LDL-C) levels in humans. The binding surface on PCSK9 is distant from its catalytic site, and the EGF-A domain makes no contact with either the C-terminal domain or the prodomain. Point mutations in PCSK9 that altered key residues contributing to EGF-A binding (Arg-194 and Phe-379) greatly diminished binding to the LDLR's extracellular domain. The structure of PCSK9 in complex with the LDLR EGF-A domain defines potential therapeutic target sites for blocking agents that could interfere with this interaction in vivo, thereby increasing LDLR function and reducing plasma LDL-C levels.
| | The line below this paragraph, {{ABSTRACT_PUBMED_18250299}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 18250299 is the PubMed ID number. |
| | --> |
| | {{ABSTRACT_PUBMED_18250299}} |
|
| |
|
| ==Disease== | | ==Disease== |
| Line 52: |
Line 56: |
| [[Category: Transport]] | | [[Category: Transport]] |
| [[Category: Zymogen]] | | [[Category: Zymogen]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 20:59:07 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 05:00:52 2008'' |