Structural changes induced by acidic pH in human apolipoprotein B-100.
Acidification in the endosome causes lipoprotein release by promoting a conformational change in the LDLR allowing its recycling and degradation of LDL. Notwithstanding conformational changes occurring in the LDLR have expanded considerably, structural changes occurring in LDL particles have not been fully explored yet. The objectives of the present work were to study structural changes occurring in apoB100 by infrared spectroscopy (IR) and also LDL size and morphology by dynamic light scattering (DLS) and electron microscopy (EM) at both pH 7.4 and 5.0. We determined by IR that pH acidification from 7.4 to 5.0, resembling that occurring within endosomal environment, induces a huge reversible structural rearrangement of apoB100 that is characterized by a reduction of beta-sheet content in favor of alpha-helix structures. Data obtained from DLS and EM showed no appreciable differences in size and morphology of LDL. These structural changes observed in apoB100, which are likely implied in particle release from lipoprotein receptor, also compromise the apoprotein stability what would facilitate LDL degradation. In conclusion, the obtained results reveal a more dynamic picture of the LDL/LDLR dissociation process than previously perceived and provide new structural insights into LDL/LDLR interactions than can occur at endosomal low-pH milieu.
Biofisika Institute (UPV/EHU, CSIC), University of the Basque Country, UPV/EHU, Spain, Apdo. 644, 48080 Bilbao, Spain.|Dpt. Biochemistry and Molecular Biology, University of the Basque Country, UPV/EHU, Spain, Apdo. 644, 48080 Bilbao, Spain.
José A
JA
Fernández-Higuero
Biofisika Institute (UPV/EHU, CSIC), University of the Basque Country, UPV/EHU, Spain, Apdo. 644, 48080 Bilbao, Spain.|Dpt. Biochemistry and Molecular Biology, University of the Basque Country, UPV/EHU, Spain, Apdo. 644, 48080 Bilbao, Spain.
Asier
A
Benito-Vicente
Biofisika Institute (UPV/EHU, CSIC), University of the Basque Country, UPV/EHU, Spain, Apdo. 644, 48080 Bilbao, Spain.|Dpt. Biochemistry and Molecular Biology, University of the Basque Country, UPV/EHU, Spain, Apdo. 644, 48080 Bilbao, Spain.
Aitor
A
Etxebarria
Dpt. Biochemistry and Molecular Biology, University of the Basque Country, UPV/EHU, Spain, Apdo. 644, 48080 Bilbao, Spain.
José Carlos G
JC
Milicua
Biofisika Institute (UPV/EHU, CSIC), University of the Basque Country, UPV/EHU, Spain, Apdo. 644, 48080 Bilbao, Spain.|Dpt. Biochemistry and Molecular Biology, University of the Basque Country, UPV/EHU, Spain, Apdo. 644, 48080 Bilbao, Spain.
Helena
H
Ostolaza
Biofisika Institute (UPV/EHU, CSIC), University of the Basque Country, UPV/EHU, Spain, Apdo. 644, 48080 Bilbao, Spain.|Dpt. Biochemistry and Molecular Biology, University of the Basque Country, UPV/EHU, Spain, Apdo. 644, 48080 Bilbao, Spain.
José L R
JL
Arrondo
Biofisika Institute (UPV/EHU, CSIC), University of the Basque Country, UPV/EHU, Spain, Apdo. 644, 48080 Bilbao, Spain.|Dpt. Biochemistry and Molecular Biology, University of the Basque Country, UPV/EHU, Spain, Apdo. 644, 48080 Bilbao, Spain.
Cesar
C
Martín
D053299:Apolipoprotein B-100 / Q000737:chemistry* / Q000378:metabolism*; D000067493:Dynamic Light Scattering; D011992:Endosomes / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008077:Lipoproteins, LDL / Q000737:chemistry / Q000378:metabolism*; D008854:Microscopy, Electron; D008958:Models, Molecular; D011485:Protein Binding; D055550:Protein Stability; D017433:Protein Structure, Secondary
C569471:APOB protein, human; D053299:Apolipoprotein B-100; D008077:Lipoproteins, LDL