| pubmed-article:18250299 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:18250299 | lifeskim:mentions | umls-concept:C0034821 | lld:lifeskim |
| pubmed-article:18250299 | lifeskim:mentions | umls-concept:C0524637 | lld:lifeskim |
| pubmed-article:18250299 | lifeskim:mentions | umls-concept:C1853126 | lld:lifeskim |
| pubmed-article:18250299 | lifeskim:mentions | umls-concept:C1426592 | lld:lifeskim |
| pubmed-article:18250299 | pubmed:issue | 6 | lld:pubmed |
| pubmed-article:18250299 | pubmed:dateCreated | 2008-2-14 | lld:pubmed |
| pubmed-article:18250299 | pubmed:databankReference | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18250299 | pubmed:abstractText | 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. | lld:pubmed |
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| pubmed-article:18250299 | pubmed:language | eng | lld:pubmed |
| pubmed-article:18250299 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18250299 | pubmed:citationSubset | IM | lld:pubmed |
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| pubmed-article:18250299 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:18250299 | pubmed:month | Feb | lld:pubmed |
| pubmed-article:18250299 | pubmed:issn | 1091-6490 | lld:pubmed |
| pubmed-article:18250299 | pubmed:author | pubmed-author:HortonJay DJD | lld:pubmed |
| pubmed-article:18250299 | pubmed:author | pubmed-author:DeisenhoferJo... | lld:pubmed |
| pubmed-article:18250299 | pubmed:author | pubmed-author:LagaceThomas... | lld:pubmed |
| pubmed-article:18250299 | pubmed:author | pubmed-author:KwonHyock... | lld:pubmed |
| pubmed-article:18250299 | pubmed:author | pubmed-author:McNuttMarkey... | lld:pubmed |
| pubmed-article:18250299 | pubmed:issnType | Electronic | lld:pubmed |
| pubmed-article:18250299 | pubmed:day | 12 | lld:pubmed |
| pubmed-article:18250299 | pubmed:volume | 105 | lld:pubmed |
| pubmed-article:18250299 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:18250299 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:18250299 | pubmed:pagination | 1820-5 | lld:pubmed |
| pubmed-article:18250299 | pubmed:dateRevised | 2009-11-18 | lld:pubmed |
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| pubmed-article:18250299 | pubmed:year | 2008 | lld:pubmed |
| pubmed-article:18250299 | pubmed:articleTitle | Molecular basis for LDL receptor recognition by PCSK9. | lld:pubmed |
| pubmed-article:18250299 | pubmed:affiliation | Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390-9050, USA. | lld:pubmed |
| pubmed-article:18250299 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:18250299 | pubmed:publicationType | Research Support, U.S. Gov't, Non-P.H.S. | lld:pubmed |
| pubmed-article:18250299 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
| pubmed-article:18250299 | pubmed:publicationType | Research Support, N.I.H., Extramural | lld:pubmed |
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