In this study, we propose a structure for the heterodimer between apolipoprotein A-I(Milano) and apolipoprotein A-II (apoA-I(M)-apoA-II) in a synthetic high-density lipoprotein (HDL) containing L-alpha-palmitoyloleoyl phosphatidylcholine. We applied bioinformatics/computational tools and procedures, such as molecular docking, molecular and essential dynamics, starting from published crystal structures for apolipoprotein A-I and apolipoprotein A-II. Structural and energetic analyses onto the simulated system showed that the molecular dynamics produced a stabilized synthetic HDL. The essential dynamic analysis showed a deviation from the starting belt structure. Our structural results were validated by limited proteolysis experiments on HDL from apoA-I(M) carriers in comparison with control HDL. The high sensitivity of apoA-I(M)-apoA-II to proteases was in agreement with the high root mean-square fluctuation values and the reduction in secondary structure content from molecular dynamics data. Circular dichroism on synthetic HDL containing apoA-I(M)-apoA-II was consistent with the alpha-helix content computed on the proposed model

A model structure for the heterodimer apoA-IMilano-apoA-II supports its peculiar susceptibility to proteolysis / A.G. Rocco, L. Mollica, E. Gianazza, L. Calabresi, G. Franceschini, C.R. Sirtori, I. Eberini, A GUERINI ROCCO. - In: BIOPHYSICAL JOURNAL. - ISSN 0006-3495. - 91:8(2006), pp. 3043-3049.

A model structure for the heterodimer apoA-IMilano-apoA-II supports its peculiar susceptibility to proteolysis

L. Mollica;E. Gianazza;L. Calabresi;G. Franceschini;C.R. Sirtori
Penultimo
;
I. Eberini
Ultimo
;
A GUERINI ROCCO
2006

Abstract

In this study, we propose a structure for the heterodimer between apolipoprotein A-I(Milano) and apolipoprotein A-II (apoA-I(M)-apoA-II) in a synthetic high-density lipoprotein (HDL) containing L-alpha-palmitoyloleoyl phosphatidylcholine. We applied bioinformatics/computational tools and procedures, such as molecular docking, molecular and essential dynamics, starting from published crystal structures for apolipoprotein A-I and apolipoprotein A-II. Structural and energetic analyses onto the simulated system showed that the molecular dynamics produced a stabilized synthetic HDL. The essential dynamic analysis showed a deviation from the starting belt structure. Our structural results were validated by limited proteolysis experiments on HDL from apoA-I(M) carriers in comparison with control HDL. The high sensitivity of apoA-I(M)-apoA-II to proteases was in agreement with the high root mean-square fluctuation values and the reduction in secondary structure content from molecular dynamics data. Circular dichroism on synthetic HDL containing apoA-I(M)-apoA-II was consistent with the alpha-helix content computed on the proposed model
Settore BIO/10 - Biochimica
Settore BIO/14 - Farmacologia
http://www.ncbi.nlm.nih.gov/entrez/utils/fref.fcgi?itool=AbstractPlus-def&PrId=3051&uid=16891368&db=pubmed&url=http://www.biophysj.org/cgi/pmidlookup?view=long&pmid=16891368
Article (author)
File in questo prodotto:
Non ci sono file associati a questo prodotto.
Pubblicazioni consigliate

Caricamento pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/23222
Citazioni
  • ???jsp.display-item.citation.pmc??? 4
  • Scopus 13
  • ???jsp.display-item.citation.isi??? 12
social impact