| Structural highlights
Disease
[APOA1_HUMAN] Defects in APOA1 are a cause of high density lipoprotein deficiency type 2 (HDLD2) [MIM:604091]; also known as familial hypoalphalipoproteinemia (FHA). Inheritance is autosomal dominant.[1] [2] Defects in APOA1 are a cause of the low HDL levels observed in high density lipoprotein deficiency type 1 (HDLD1) [MIM:205400]; also known as analphalipoproteinemia or Tangier disease (TGD). HDLD1 is a recessive disorder characterized by the absence of plasma HDL, accumulation of cholesteryl esters, premature coronary artery disease, hepatosplenomegaly, recurrent peripheral neuropathy and progressive muscle wasting and weakness. In HDLD1 patients, ApoA-I fails to associate with HDL probably because of the faulty conversion of pro-ApoA-I molecules into mature chains, either due to a defect in the converting enzyme activity or a specific structural defect in Tangier ApoA-I.[3] [4] Note=A mutation in APOA1 is the cause of amyloid polyneuropathy-nephropathy Iowa type (AMYLIOWA); also known as amyloidosis van Allen type or familial amyloid polyneuropathy type III. AMYLIOWA is a hereditary generalized amyloidosis due to deposition of amyloid mainly constituted by apolipoprotein A1. The clinical picture is dominated by neuropathy in the early stages of the disease and nephropathy late in the course. Death is due in most cases to renal amyloidosis. Severe peptic ulcer disease can occurr in some and hearing loss is frequent. Cataracts is present in several, but vitreous opacities are not observed.[5] [6] [7] [8] Defects in APOA1 are a cause of amyloidosis type 8 (AMYL8) [MIM:105200]; also known as systemic non-neuropathic amyloidosis or Ostertag-type amyloidosis. AMYL8 is a hereditary generalized amyloidosis due to deposition of apolipoprotein A1, fibrinogen and lysozyme amyloids. Viscera are particularly affected. There is no involvement of the nervous system. Clinical features include renal amyloidosis resulting in nephrotic syndrome, arterial hypertension, hepatosplenomegaly, cholestasis, petechial skin rash.[9] [10] [11]
Function
[MMP14_HUMAN] Seems to specifically activate progelatinase A. May thus trigger invasion by tumor cells by activating progelatinase A on the tumor cell surface. May be involved in actin cytoskeleton reorganization by cleaving PTK7. Acts as a positive regulator of cell growth and migration via activation of MMP15.[12] [13] [APOA1_HUMAN] Participates in the reverse transport of cholesterol from tissues to the liver for excretion by promoting cholesterol efflux from tissues and by acting as a cofactor for the lecithin cholesterol acyltransferase (LCAT). As part of the SPAP complex, activates spermatozoa motility.[14]
Publication Abstract from PubMed
Critical to migration of tumor cells and endothelial cells is the proteolytic attack of membrane type 1 matrix metalloproteinase (MT1-MMP) upon collagen, growth factors, and receptors at cell surfaces. Lipid bilayer interactions of the substrate-binding hemopexin-like (HPX) domain of MT1-MMP were investigated by paramagnetic nuclear magnetic resonance relaxation enhancements (PREs), fluorescence, and mutagenesis. The HPX domain binds bilayers by blades II and IV on opposite sides of its beta propeller fold. The EPGYPK sequence protruding from both blades inserts among phospholipid head groups in PRE-restrained molecular dynamics simulations. Bilayer binding to either blade II or IV exposes the CD44 binding site in blade I. Bilayer association with blade IV allows the collagen triple helix to bind without obstruction. Indeed, vesicles enhance proteolysis of collagen triple-helical substrates by the ectodomain of MT1-MMP. Hypothesized side-by-side MT1-MMP homodimerization would allow binding of bilayers, collagen, CD44, and head-to-tail oligomerization.
MT1-MMP Binds Membranes by Opposite Tips of Its beta Propeller to Position It for Pericellular Proteolysis.,Marcink TC, Simoncic JA, An B, Knapinska AM, Fulcher YG, Akkaladevi N, Fields GB, Van Doren SR Structure. 2018 Nov 21. pii: S0969-2126(18)30369-1. doi:, 10.1016/j.str.2018.10.008. PMID:30471921[15]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Nakata K, Kobayashi K, Yanagi H, Shimakura Y, Tsuchiya S, Arinami T, Hamaguchi H. Autosomal dominant hypoalphalipoproteinemia due to a completely defective apolipoprotein A-I gene. Biochem Biophys Res Commun. 1993 Oct 29;196(2):950-5. PMID:8240372 doi:http://dx.doi.org/S0006-291X(83)72341-7
- ↑ Ng DS, Leiter LA, Vezina C, Connelly PW, Hegele RA. Apolipoprotein A-I Q[-2]X causing isolated apolipoprotein A-I deficiency in a family with analphalipoproteinemia. J Clin Invest. 1994 Jan;93(1):223-9. PMID:8282791 doi:http://dx.doi.org/10.1172/JCI116949
- ↑ Nakata K, Kobayashi K, Yanagi H, Shimakura Y, Tsuchiya S, Arinami T, Hamaguchi H. Autosomal dominant hypoalphalipoproteinemia due to a completely defective apolipoprotein A-I gene. Biochem Biophys Res Commun. 1993 Oct 29;196(2):950-5. PMID:8240372 doi:http://dx.doi.org/S0006-291X(83)72341-7
- ↑ Ng DS, Leiter LA, Vezina C, Connelly PW, Hegele RA. Apolipoprotein A-I Q[-2]X causing isolated apolipoprotein A-I deficiency in a family with analphalipoproteinemia. J Clin Invest. 1994 Jan;93(1):223-9. PMID:8282791 doi:http://dx.doi.org/10.1172/JCI116949
- ↑ Nakata K, Kobayashi K, Yanagi H, Shimakura Y, Tsuchiya S, Arinami T, Hamaguchi H. Autosomal dominant hypoalphalipoproteinemia due to a completely defective apolipoprotein A-I gene. Biochem Biophys Res Commun. 1993 Oct 29;196(2):950-5. PMID:8240372 doi:http://dx.doi.org/S0006-291X(83)72341-7
- ↑ Ng DS, Leiter LA, Vezina C, Connelly PW, Hegele RA. Apolipoprotein A-I Q[-2]X causing isolated apolipoprotein A-I deficiency in a family with analphalipoproteinemia. J Clin Invest. 1994 Jan;93(1):223-9. PMID:8282791 doi:http://dx.doi.org/10.1172/JCI116949
- ↑ Nichols WC, Dwulet FE, Liepnieks J, Benson MD. Variant apolipoprotein AI as a major constituent of a human hereditary amyloid. Biochem Biophys Res Commun. 1988 Oct 31;156(2):762-8. PMID:3142462
- ↑ Nichols WC, Gregg RE, Brewer HB Jr, Benson MD. A mutation in apolipoprotein A-I in the Iowa type of familial amyloidotic polyneuropathy. Genomics. 1990 Oct;8(2):318-23. PMID:2123470
- ↑ Nakata K, Kobayashi K, Yanagi H, Shimakura Y, Tsuchiya S, Arinami T, Hamaguchi H. Autosomal dominant hypoalphalipoproteinemia due to a completely defective apolipoprotein A-I gene. Biochem Biophys Res Commun. 1993 Oct 29;196(2):950-5. PMID:8240372 doi:http://dx.doi.org/S0006-291X(83)72341-7
- ↑ Ng DS, Leiter LA, Vezina C, Connelly PW, Hegele RA. Apolipoprotein A-I Q[-2]X causing isolated apolipoprotein A-I deficiency in a family with analphalipoproteinemia. J Clin Invest. 1994 Jan;93(1):223-9. PMID:8282791 doi:http://dx.doi.org/10.1172/JCI116949
- ↑ Soutar AK, Hawkins PN, Vigushin DM, Tennent GA, Booth SE, Hutton T, Nguyen O, Totty NF, Feest TG, Hsuan JJ, et al.. Apolipoprotein AI mutation Arg-60 causes autosomal dominant amyloidosis. Proc Natl Acad Sci U S A. 1992 Aug 15;89(16):7389-93. PMID:1502149
- ↑ Golubkov VS, Chekanov AV, Cieplak P, Aleshin AE, Chernov AV, Zhu W, Radichev IA, Zhang D, Dong PD, Strongin AY. The Wnt/planar cell polarity protein-tyrosine kinase-7 (PTK7) is a highly efficient proteolytic target of membrane type-1 matrix metalloproteinase: implications in cancer and embryogenesis. J Biol Chem. 2010 Nov 12;285(46):35740-9. doi: 10.1074/jbc.M110.165159. Epub 2010, Sep 13. PMID:20837484 doi:http://dx.doi.org/10.1074/jbc.M110.165159
- ↑ Gu G, Zhao D, Yin Z, Liu P. BST-2 binding with cellular MT1-MMP blocks cell growth and migration via decreasing MMP2 activity. J Cell Biochem. 2012 Mar;113(3):1013-21. doi: 10.1002/jcb.23433. PMID:22065321 doi:10.1002/jcb.23433
- ↑ Akerlof E, Jornvall H, Slotte H, Pousette A. Identification of apolipoprotein A1 and immunoglobulin as components of a serum complex that mediates activation of human sperm motility. Biochemistry. 1991 Sep 17;30(37):8986-90. PMID:1909888
- ↑ Marcink TC, Simoncic JA, An B, Knapinska AM, Fulcher YG, Akkaladevi N, Fields GB, Van Doren SR. MT1-MMP Binds Membranes by Opposite Tips of Its beta Propeller to Position It for Pericellular Proteolysis. Structure. 2018 Nov 21. pii: S0969-2126(18)30369-1. doi:, 10.1016/j.str.2018.10.008. PMID:30471921 doi:http://dx.doi.org/10.1016/j.str.2018.10.008
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