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词条 Apolipoprotein H
释义

  1. Inhibitory activities

  2. Pathology

  3. Sushi 2 protein domain

     Structure  Function 

  4. References

  5. External links

{{Infobox_gene}}Apolipoprotein H (Apo-H), previously known as β2-glycoprotein I and beta-2 glycoprotein I, is a 38 kDa multifunctional apolipoprotein that in humans is encoded by the APOH gene{{Citation needed|date=November 2015}}. One of its functions is to bind cardiolipin. When bound the structure of cardiolipin and Apo-H both undergo large changes in structure.[1] Within the structure of Apo-H is a stretch of positively charged amino acids (protein sequence positions 282-287), Lys-Asn-Lys-Glu-Lys-Lys, are involved in phospholipid binding (See image on right).[2]

Apo-H has a complex involvement in agglutination, it appears to alter adenosine diphosphate (ADP) mediated agglutination of platelets.[3] Normally Apo-H assumes an anti-coagulation activity in serum (by inhibiting coagulation factors); however, changes in blood factors can result of a reversal of that activity.

Inhibitory activities

Apo-H appears to completely inhibit serotonin release by the platelets[4] and prevents subsequent waves of the ADP-induced aggregation. The activity of Apo-H appears to involve the binding of agglutinating, negatively charged compounds, and inhibits agglutination by the contact activation of the intrinsic blood coagulation pathway.[5] Apo-H causes a reduction of the prothrombinase binding sites on platelets and reduces the activation caused by collagen when thrombin is present at physiological serum concentrations of Apo-H suggesting a regulatory role of Apo-H in coagulation.[6]

Apo-H also inhibits the generation of factor Xa in the presence of platelets.[7] Apo-H also inhibits that activation of factor XIIa.[8]

In addition, Apo-H inhibits the activation of protein C blocking its activity on phosphatidylserine:phosphatidylcholine vesicles[9] however once protein C is activated, Apo-H fails to inhibit activity. Since protein C is involved in factor Va degradation Apo-H indirectly inhibits the degradation of factor Va.[10] This inhibitory activity was diminished by adding phospholipids suggesting the Apo-H inhibition of protein C is phospholipid competitive.[11] This indicates that under certain conditions Apo-H takes on a procoagulation properties.

Pathology

Anti-cardiolipin antibodies are found in both infectious and some systemic autoimmune diseases (eg. systemic sclerosis (scleroderma), systemic lupus erythematosus (SLE)).[12] One having anti-cardiolipin antibodies shows false positivity in the syphilis test as it is performed with the antigen bound to cardiolipin surface, which anti-cardiolipin antibodies can cross-react with. The activity of anti-cardiolipin antibodies in autoimmune antiphospholipid syndrome requires apolipoprotein H.[13][14] The subset of antibodies that bind Apo-H and alter its activity are considered different from antibodies that bind thrombin, serum phospholipids and are called anti-apolipoprotein antibodies. In autoimmune disease, anti-apolipoprotein antibodies (Anti β2 glycoprotein I antibodies) strongly associate with thrombotic forms of lupus and sclerosis.

Sushi 2 protein domain

{{Infobox protein family
| Symbol = Sushi_2
| Name = Sushi_2
| image = PDB 1g4g EBI.jpg
| width =
| caption = NMR structure of the fifth domain of human beta-2-glycoprotein I
| Pfam = PF09014
| Pfam_clan =
| InterPro = IPR015104
| SMART =
| PROSITE =
| MEROPS =
| SCOP =
| TCDB =
| OPM family =
| OPM protein =
| CAZy =
| CDD =
}}

In molecular biology, the protein domain Sushi 2 is also known as the fifth protein domain of beta-2-glycoprotein-1 (b2GP-1). This protein domain is only found in eukaryotes. The first four domains found in Apolipoprotein H resemble each other, however the fifth one appears to be different.[15]

Structure

This protein domain is composed of four well-defined anti-parallel beta-strands and two short alpha-helices, as well as a long highly flexible loop.[16] Additionally, the fifth protein domain appears to resemble the other four in Apolipoprotein with the exception of three internal disulfide bonds and an extra C-terminal loop.[15]

Function

Its exact function remains to be fully elucidated, however it is known to play an important role in the binding of b2GP-1 to negatively charged compounds and subsequent capture for binding of anti-b2GP-1 antibodies.[16] Problems such as a mutation in this protein would lead to Antiphospholipid syndrome which often leads to pregnancy complications.[15]

References

1. ^{{cite journal |vauthors=Borchman D, Harris EN, Pierangeli SS, Lamba OP | title = Interactions and molecular structure of cardiolipin and beta 2-glycoprotein 1 (beta 2-GP1) | journal = Clin. Exp. Immunol. | volume = 102 | issue = 2 | pages = 373–8 | year = 1995 | pmid = 7586693 | doi = 10.1111/j.1365-2249.1995.tb03792.x| pmc = 1553418 }}
2. ^{{cite journal |vauthors=Sheng Y, Sali A, Herzog H, Lahnstein J, Krilis SA | title = Site-directed mutagenesis of recombinant human beta 2-glycoprotein I identifies a cluster of lysine residues that are critical for phospholipid binding and anti-cardiolipin antibody activity | journal = J. Immunol. | volume = 157 | issue = 8 | pages = 3744–51 | year = 1996 | pmid = 8871678 | doi = }}
3. ^{{cite journal |vauthors=Nimpf J, Wurm H, Kostner GM | title = Interaction of beta 2-glycoprotein-I with human blood platelets: influence upon the ADP-induced aggregation | journal = Thromb. Haemost. | volume = 54 | issue = 2 | pages = 397–401 | year = 1985 | pmid = 4082080 | doi = }}
4. ^{{cite journal |vauthors=Nimpf J, Wurm H, Kostner GM | title = Beta 2-glycoprotein-I (apo-H) inhibits the release reaction of human platelets during ADP-induced aggregation | journal = Atherosclerosis | volume = 63 | issue = 2–3 | pages = 109–14 | year = 1987 | pmid = 3827975 | doi =10.1016/0021-9150(87)90110-9 }}
5. ^{{cite journal | author = Schousboe I | title = beta 2-Glycoprotein I: a plasma inhibitor of the contact activation of the intrinsic blood coagulation pathway | journal = Blood | volume = 66 | issue = 5 | pages = 1086–91 | year = 1985 | pmid = 4052628 | doi = }}
6. ^{{cite journal |vauthors=Nimpf J, Bevers EM, Bomans PH | title = Prothrombinase activity of human platelets is inhibited by beta 2-glycoprotein-I | journal = Biochim. Biophys. Acta | volume = 884 | issue = 1 | pages = 142–9 | year = 1986 | pmid = 3768409 | doi = 10.1016/0304-4165(86)90237-0|display-authors=etal}}
7. ^{{cite journal |vauthors=Shi W, Chong BH, Hogg PJ, Chesterman CN | title = Anticardiolipin antibodies block the inhibition by beta 2-glycoprotein I of the factor Xa generating activity of platelets | journal = Thromb. Haemost. | volume = 70 | issue = 2 | pages = 342–5 | year = 1993 | pmid = 8236146 | doi = }}
8. ^{{cite journal |vauthors=Schousboe I, Rasmussen MS | title = Synchronized inhibition of the phospholipid mediated autoactivation of factor XII in plasma by beta 2-glycoprotein I and anti-beta 2-glycoprotein I | journal = Thromb. Haemost. | volume = 73 | issue = 5 | pages = 798–804 | year = 1995 | pmid = 7482406 | doi = }}
9. ^{{cite journal |vauthors=Keeling DM, Wilson AJ, Mackie IJ, Isenberg DA, Machin SJ | title = Role of beta 2-glycoprotein I and anti-phospholipid antibodies in activation of protein C in vitro | journal = J. Clin. Pathol. | volume = 46 | issue = 10 | pages = 908–11 | year = 1993 | pmid = 8227406 | doi =10.1136/jcp.46.10.908 | pmc = 501616 }}
10. ^{{cite journal |vauthors=Matsuda J, Gohchi K, Kawasugi K, Gotoh M, Saitoh N, Tsukamoto M | title = Inhibitory activity of anti-beta 2-glycoprotein I antibody on factor Va degradation by activated-protein C and its cofactor protein S | journal = Am. J. Hematol. | volume = 49 | issue = 1 | pages = 89–91 | year = 1995 | pmid = 7741146 | doi =10.1002/ajh.2830490116 }}
11. ^{{cite journal |vauthors=Mori T, Takeya H, Nishioka J, Gabazza EC, Suzuki K | title = beta 2-Glycoprotein I modulates the anticoagulant activity of activated protein C on the phospholipid surface | journal = Thromb. Haemost. | volume = 75 | issue = 1 | pages = 49–55 | year = 1996 | pmid = 8713779 | doi = }}
12. ^{{cite journal|vauthors=Kumar KS, Jyothy A, Prakash MS, Rani HS, Reddy PP|year=2002|title=Beta2-glycoprotein I dependent anticardiolipin antibodies and lupus anticoagulant in patients with recurrent pregnancy loss|journal=Journal of Postgraduate Medicine|volume=48|issue=1|pages=5–10|doi=|pmid=12082318}}
13. ^{{cite journal |vauthors=McNeil HP, Simpson RJ, Chesterman CN, Krilis SA | title = Anti-phospholipid antibodies are directed against a complex antigen that includes a lipid-binding inhibitor of coagulation: beta 2-glycoprotein I (apolipoprotein H) | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 87 | issue = 11 | pages = 4120–4 | year = 1990 | pmid = 2349221 | doi =10.1073/pnas.87.11.4120 | pmc = 54059 }}
14. ^{{cite journal |vauthors=Hunt JE, McNeil HP, Morgan GJ, Crameri RM, Krilis SA | title = A phospholipid-beta 2-glycoprotein I complex is an antigen for anticardiolipin antibodies occurring in autoimmune disease but not with infection | journal = Lupus | volume = 1 | issue = 2 | pages = 75–81 | year = 1992 | pmid = 1301967 | doi =10.1177/096120339200100204 }}
15. ^1 2 {{cite journal|vauthors=Shi T, Giannakopoulos B, Iverson GM, Cockerill KA, Linnik MD, Krilis SA | title=Domain V of beta2-glycoprotein I binds factor XI/XIa and is cleaved at Lys317-Thr318. | journal=J Biol Chem | year= 2005 | volume= 280 | issue= 2 | pages= 907–12 | pmid=15522884 | doi=10.1074/jbc.M410291200 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15522884 }}
16. ^1 {{cite journal |vauthors=Hoshino M, Hagihara Y, Nishii I, Yamazaki T, Kato H, Goto Y | title = Identification of the phospholipid-binding site of human beta(2)-glycoprotein I domain V by heteronuclear magnetic resonance | journal = J. Mol. Biol. | volume = 304 | issue = 5 | pages = 927–39 |date=December 2000 | pmid = 11124037 | doi = 10.1006/jmbi.2000.4243 | url = }}

External links

  • {{MeshName|Apolipoprotein+H}}
  • [https://www.mabtech.com/knowledge-center/applied-research/apolipoproteins Apolipoprotein H and Applied Research]
  • {{UCSC gene info|APOH}}
{{Autoantigens}}{{Lipoproteins}}{{Glycoproteins}}

3 : Autoimmune diseases|Apolipoproteins|Autoantigens
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