Matches in SemOpenAlex for { <https://semopenalex.org/work/W2061006840> ?p ?o ?g. }
Showing items 1 to 73 of
73
with 100 items per page.
- W2061006840 endingPage "36a" @default.
- W2061006840 startingPage "36a" @default.
- W2061006840 abstract "Human cholesteryl ester transfer protein (CETP), a hydrophobic glycoprotein (476 amino acids, ∼74 kDa), mediates the transfer of cholesteryl ester (CE) from high-density lipoproteins (HDL) to apo-B containing lipoproteins (low-density lipoproteins - LDL; very low density lipoproteins - VLDL). The crystal structure of CETP reveals a banana-shaped protein consisting of N- and C-terminal β-barrel domains, a central β-sheet, and a ∼60-Å-long hydrophobic cavity. Since CETP deficiency is associated with elevated ‘good-cholesterol’ (HDL-associated) levels via delayed catabolism, as a result, CETP has become a high interest pharmacological drug target. Here, we investigated the mechanism of CETP-mediated neutral lipid transfer by electron microscopy (EM), image-processing, and molecular dynamic simulations (MDS). We discovered that: 1) CETP bridges HDL and LDL/VLDL to form a ternary complex; 2) the CETP C-terminal beta-barrel domain penetrates partially into the LDL/VLDL surface; 3) the N-terminal beta-barrel domain penetrates through the HDL surface and interacts with the CE core; and 4) MDS analysis suggested that the penetrating regions of CETP are highly mobile and form pores that connect to cavities running through the central axis of the CETP molecule to generate a tunnel. The tunnel was mainly hydrophobic and connected the distal ends through its central cavities. Thus, we proposed CETP resembles a Chinese finger trap, in which both beta-barrel domains penetrate the lipoprotein surface, resulting in pressure from both ends. The pressure may result in the anti-twisting of the two domains, leading to opening of the tunnel for CE transfer between HDL and LDL. The distal end of N-terminal beta-barrel domain could be particularly important for the design of pharmacological inhibitors, as blockage of the N-terminal beta-barrel domain would prevent CE transfer with a low probability of off target effects on normal HDL metabolism." @default.
- W2061006840 created "2016-06-24" @default.
- W2061006840 creator A5033190041 @default.
- W2061006840 creator A5036760591 @default.
- W2061006840 creator A5044927871 @default.
- W2061006840 creator A5049081447 @default.
- W2061006840 creator A5054426322 @default.
- W2061006840 creator A5055223538 @default.
- W2061006840 creator A5059463745 @default.
- W2061006840 creator A5079558596 @default.
- W2061006840 creator A5084603339 @default.
- W2061006840 date "2010-01-01" @default.
- W2061006840 modified "2023-10-16" @default.
- W2061006840 title "Cholesteryl Ester Transfer Protein Penetrates Lipoproteins For Cholesteryl Ester Transfer" @default.
- W2061006840 doi "https://doi.org/10.1016/j.bpj.2009.12.212" @default.
- W2061006840 hasPublicationYear "2010" @default.
- W2061006840 type Work @default.
- W2061006840 sameAs 2061006840 @default.
- W2061006840 citedByCount "2" @default.
- W2061006840 countsByYear W20610068402012 @default.
- W2061006840 countsByYear W20610068402019 @default.
- W2061006840 crossrefType "journal-article" @default.
- W2061006840 hasAuthorship W2061006840A5033190041 @default.
- W2061006840 hasAuthorship W2061006840A5036760591 @default.
- W2061006840 hasAuthorship W2061006840A5044927871 @default.
- W2061006840 hasAuthorship W2061006840A5049081447 @default.
- W2061006840 hasAuthorship W2061006840A5054426322 @default.
- W2061006840 hasAuthorship W2061006840A5055223538 @default.
- W2061006840 hasAuthorship W2061006840A5059463745 @default.
- W2061006840 hasAuthorship W2061006840A5079558596 @default.
- W2061006840 hasAuthorship W2061006840A5084603339 @default.
- W2061006840 hasBestOaLocation W20610068401 @default.
- W2061006840 hasConcept C12554922 @default.
- W2061006840 hasConcept C185592680 @default.
- W2061006840 hasConcept C2776448209 @default.
- W2061006840 hasConcept C2778163477 @default.
- W2061006840 hasConcept C2780072125 @default.
- W2061006840 hasConcept C45505151 @default.
- W2061006840 hasConcept C55493867 @default.
- W2061006840 hasConcept C8004288 @default.
- W2061006840 hasConcept C8243546 @default.
- W2061006840 hasConcept C86803240 @default.
- W2061006840 hasConceptScore W2061006840C12554922 @default.
- W2061006840 hasConceptScore W2061006840C185592680 @default.
- W2061006840 hasConceptScore W2061006840C2776448209 @default.
- W2061006840 hasConceptScore W2061006840C2778163477 @default.
- W2061006840 hasConceptScore W2061006840C2780072125 @default.
- W2061006840 hasConceptScore W2061006840C45505151 @default.
- W2061006840 hasConceptScore W2061006840C55493867 @default.
- W2061006840 hasConceptScore W2061006840C8004288 @default.
- W2061006840 hasConceptScore W2061006840C8243546 @default.
- W2061006840 hasConceptScore W2061006840C86803240 @default.
- W2061006840 hasIssue "3" @default.
- W2061006840 hasLocation W20610068401 @default.
- W2061006840 hasOpenAccess W2061006840 @default.
- W2061006840 hasPrimaryLocation W20610068401 @default.
- W2061006840 hasRelatedWork W1491900378 @default.
- W2061006840 hasRelatedWork W195600153 @default.
- W2061006840 hasRelatedWork W1984154504 @default.
- W2061006840 hasRelatedWork W2003671495 @default.
- W2061006840 hasRelatedWork W2054827051 @default.
- W2061006840 hasRelatedWork W2122454094 @default.
- W2061006840 hasRelatedWork W2161003745 @default.
- W2061006840 hasRelatedWork W2414598648 @default.
- W2061006840 hasRelatedWork W2419231413 @default.
- W2061006840 hasRelatedWork W3036866 @default.
- W2061006840 hasVolume "98" @default.
- W2061006840 isParatext "false" @default.
- W2061006840 isRetracted "false" @default.
- W2061006840 magId "2061006840" @default.
- W2061006840 workType "article" @default.