Proposed lipocalin fold for apolipoprotein M based on bioinformatics and site-directed mutagenesis.
Apolipoprotein M (apoM) is a novel apolipoprotein that is predominantly present in high-density lipoprotein. Sensitive sequence searches, threading and comparative model building experiments revealed apoM to be structurally related to the lipocalin protein family. In a 3D model, characterized by an eight-stranded anti-parallel beta-barrel, a segment including Asn135 could adopt a closed or open conformation. Using site-directed mutagenesis, we demonstrated Asn135 in wild-type apoM to be glycosylated, suggesting that the segment is solvent exposed. ApoM displays two strong acidic patches of potential functional importance, one around the N-terminus and the other next to the opening of the beta-barrel.
Duan
J
J
Center for Structural Biochemistry, Department of Biosciences at Novum, Karolinska Institute, Huddinge, Sweden. jianxin.duan@csb.ki.se
Dahlbäck
B
B
Villoutreix
B O
BO
D000595:Amino Acid Sequence; D001053:Apolipoproteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D000075243:Apolipoproteins M; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D019295:Computational Biology; D003198:Computer Simulation; D019992:Databases as Topic; D029968:Escherichia coli Proteins; D006031:Glycosylation; D006801:Humans; D054834:Lipocalins; D008074:Lipoproteins / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D011487:Protein Conformation; D017510:Protein Folding; D012997:Solvents; D055672:Static Electricity; D013329:Structure-Activity Relationship
C400523:APOM protein, human; D001053:Apolipoproteins; D000075243:Apolipoproteins M; D001425:Bacterial Outer Membrane Proteins; D029968:Escherichia coli Proteins; D054834:Lipocalins; D008074:Lipoproteins; D012997:Solvents; C095894:blc protein, E coli