5okl

Human afamin monoclinic crystal formHuman afamin monoclinic crystal form

Structural highlights

5okl is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.09Å
Ligands:	, , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

AFAM_HUMAN Vitamin E binding protein. May transport vitamin E in body fluids under conditions where the lipoprotein system is not sufficient. May be involved in the regulation and transport of vitamin E at the blood-brain barrier.^[1] ^[2] ^[3]

Publication Abstract from PubMed

Afamin, a human plasma glycoprotein and putative transporter of hydrophobic molecules, has been shown to act as extracellular chaperone for poorly soluble, acylated Wnt proteins, forming a stable, soluble complex with functioning Wnt proteins. The 2.1-A crystal structure of glycosylated human afamin reveals an almost exclusively hydrophobic binding cleft capable of harboring large hydrophobic moieties. Lipid analysis confirms the presence of lipids, and density in the primary binding pocket of afamin was modeled as palmitoleic acid, presenting the native O-acylation on serine 209 in human Wnt3a. The modeled complex between the experimental afamin structure and a Wnt3a homology model based on the XWnt8-Fz8-CRD fragment complex crystal structure is compelling, with favorable interactions comparable with the crystal structure complex. Afamin readily accommodates the conserved palmitoylated serine 209 of Wnt3a, providing a structural basis how afamin solubilizes hydrophobic and poorly soluble Wnt proteins.

Structural Evidence for a Role of the Multi-functional Human Glycoprotein Afamin in Wnt Transport.,Naschberger A, Orry A, Lechner S, Bowler MW, Nurizzo D, Novokmet M, Keller MA, Oemer G, Seppi D, Haslbeck M, Pansi K, Dieplinger H, Rupp B Structure. 2017 Nov 13. pii: S0969-2126(17)30334-9. doi:, 10.1016/j.str.2017.10.006. PMID:29153507^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Voegele AF, Jerkovic L, Wellenzohn B, Eller P, Kronenberg F, Liedl KR, Dieplinger H. Characterization of the vitamin E-binding properties of human plasma afamin. Biochemistry. 2002 Dec 10;41(49):14532-8. PMID:12463752
↑ Jerkovic L, Voegele AF, Chwatal S, Kronenberg F, Radcliffe CM, Wormald MR, Lobentanz EM, Ezeh B, Eller P, Dejori N, Dieplinger B, Lottspeich F, Sattler W, Uhr M, Mechtler K, Dwek RA, Rudd PM, Baier G, Dieplinger H. Afamin is a novel human vitamin E-binding glycoprotein characterization and in vitro expression. J Proteome Res. 2005 May-Jun;4(3):889-99. doi: 10.1021/pr0500105. PMID:15952736 doi:http://dx.doi.org/10.1021/pr0500105
↑ Kratzer I, Bernhart E, Wintersperger A, Hammer A, Waltl S, Malle E, Sperk G, Wietzorrek G, Dieplinger H, Sattler W. Afamin is synthesized by cerebrovascular endothelial cells and mediates alpha-tocopherol transport across an in vitro model of the blood-brain barrier. J Neurochem. 2009 Feb;108(3):707-18. doi: 10.1111/j.1471-4159.2008.05796.x. Epub , 2008 Nov 27. PMID:19046407 doi:http://dx.doi.org/10.1111/j.1471-4159.2008.05796.x
↑ Naschberger A, Orry A, Lechner S, Bowler MW, Nurizzo D, Novokmet M, Keller MA, Oemer G, Seppi D, Haslbeck M, Pansi K, Dieplinger H, Rupp B. Structural Evidence for a Role of the Multi-functional Human Glycoprotein Afamin in Wnt Transport. Structure. 2017 Nov 13. pii: S0969-2126(17)30334-9. doi:, 10.1016/j.str.2017.10.006. PMID:29153507 doi:http://dx.doi.org/10.1016/j.str.2017.10.006

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OCA

[1] Voegele AF, Jerkovic L, Wellenzohn B, Eller P, Kronenberg F, Liedl KR, Dieplinger H. Characterization of the vitamin E-binding properties of human plasma afamin. Biochemistry. 2002 Dec 10;41(49):14532-8. PMID:12463752

[2] Jerkovic L, Voegele AF, Chwatal S, Kronenberg F, Radcliffe CM, Wormald MR, Lobentanz EM, Ezeh B, Eller P, Dejori N, Dieplinger B, Lottspeich F, Sattler W, Uhr M, Mechtler K, Dwek RA, Rudd PM, Baier G, Dieplinger H. Afamin is a novel human vitamin E-binding glycoprotein characterization and in vitro expression. J Proteome Res. 2005 May-Jun;4(3):889-99. doi: 10.1021/pr0500105. PMID:15952736 doi:http://dx.doi.org/10.1021/pr0500105

[3] Kratzer I, Bernhart E, Wintersperger A, Hammer A, Waltl S, Malle E, Sperk G, Wietzorrek G, Dieplinger H, Sattler W. Afamin is synthesized by cerebrovascular endothelial cells and mediates alpha-tocopherol transport across an in vitro model of the blood-brain barrier. J Neurochem. 2009 Feb;108(3):707-18. doi: 10.1111/j.1471-4159.2008.05796.x. Epub , 2008 Nov 27. PMID:19046407 doi:http://dx.doi.org/10.1111/j.1471-4159.2008.05796.x

[4] Naschberger A, Orry A, Lechner S, Bowler MW, Nurizzo D, Novokmet M, Keller MA, Oemer G, Seppi D, Haslbeck M, Pansi K, Dieplinger H, Rupp B. Structural Evidence for a Role of the Multi-functional Human Glycoprotein Afamin in Wnt Transport. Structure. 2017 Nov 13. pii: S0969-2126(17)30334-9. doi:, 10.1016/j.str.2017.10.006. PMID:29153507 doi:http://dx.doi.org/10.1016/j.str.2017.10.006

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