The structure of vitellogenin provides a molecular model for the assembly and secretion of atherogenic lipoproteins.
The assembly of atherogenic lipoproteins requires the formation in the endoplasmic reticulum of a complex between apolipoprotein (apo)B, a microsomal triglyceride transfer protein (MTP) and protein disulphide isomerase (PDI). Here we show by molecular modelling and mutagenesis that the globular amino-terminal regions of apoB and MTP are closely related in structure to the ancient egg yolk storage protein, vitellogenin (VTG). In the MTP complex, conserved structural motifs that form the reciprocal homodimerization interfaces in VTG are re-utilized by MTP to form a stable heterodimer with PDI, which anchors MTP at the site of apoB translocation, and to associate with apoB and initiate lipid transfer. The structural and functional evolution of the VTGs provides a unifying scheme for the invertebrate origins of the major vertebrate lipid transport system.
Mann
C J
CJ
MRC Molecular Medicine Group, Imperial College School of Medicine, London W12 ONN, UK.
Anderson
T A
TA
Read
J
J
Chester
S A
SA
Harrison
G B
GB
Köchl
S
S
Ritchie
P J
PJ
Bradbury
P
P
Hussain
F S
FS
Amey
J
J
Vanloo
B
B
Rosseneu
M
M
Infante
R
R
Hancock
J M
JM
Levitt
D G
DG
Banaszak
L J
LJ
Scott
J
J
Shoulders
C C
CC
D000595:Amino Acid Sequence; D000818:Animals; D001055:Apolipoproteins B / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D019556:COS Cells; D002352:Carrier Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D017124:Conserved Sequence; D004331:Drosophila melanogaster; D004527:Egg Proteins; D015387:Egg Proteins, Dietary / Q000032:analysis; D006801:Humans; D008074:Lipoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016296:Mutagenesis; D011487:Protein Conformation; D019704:Protein Disulfide-Isomerases / Q000378:metabolism; D014819:Vitellogenins / Q000737:chemistry* / Q000145:classification / Q000235:genetics
D001055:Apolipoproteins B; D002352:Carrier Proteins; D004527:Egg Proteins; D015387:Egg Proteins, Dietary; D008074:Lipoproteins; D014819:Vitellogenins; C106092:microsomal triglyceride transfer protein; C001549:lipovitellin; D019704:Protein Disulfide-Isomerases