| Structural highlights
Disease
ATS13_HUMAN Defects in ADAMTS13 are the cause of thrombotic thrombocytopenic purpura congenital (TTP) [MIM:274150; also known as Upshaw-Schulman syndrome (USS). A hematologic disease characterized by hemolytic anemia with fragmentation of erythrocytes, thrombocytopenia, diffuse and non-focal neurologic findings, decreased renal function and fever.[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17] [18] [19] [20]
Function
MALE_ECOLI Involved in the high-affinity maltose membrane transport system MalEFGK. Initial receptor for the active transport of and chemotaxis toward maltooligosaccharides.ATS13_HUMAN Cleaves the vWF multimers in plasma into smaller forms.
Publication Abstract from PubMed
ADAMTS13 is a plasma metalloprotease that is essential for the regulation of von Willebrand factor (VWF) function, mediator of platelet recruitment to sites of blood vessel damage. ADAMTS13 function is dynamically regulated by structural changes induced by VWF binding that convert it from a latent to active conformation. ADAMTS13 global latency is manifest by the interaction of its C-terminal CUB1-2 domains with its central Spacer domain. We resolved the crystal structure of the ADAMTS13 CUB1-2 domains revealing a previously unreported configuration for the tandem CUB domains. Docking simulations between the CUB1-2 domains with the Spacer domain in combination with enzyme kinetic functional characterization of ADAMTS13 CUB domain mutants enabled the mapping of the CUB1-2 domain site that binds the Spacer domain. Together, these data reveal the molecular basis of the ADAMTS13 Spacer-CUB interaction and the control of ADAMTS13 global latency.
Crystal structure of ADAMTS13 CUB domains reveals their role in global latency.,Kim HJ, Xu Y, Petri A, Vanhoorelbeke K, Crawley JTB, Emsley J Sci Adv. 2021 Apr 16;7(16). pii: 7/16/eabg4403. doi: 10.1126/sciadv.abg4403., Print 2021 Apr. PMID:33863735[21]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Levy GG, Nichols WC, Lian EC, Foroud T, McClintick JN, McGee BM, Yang AY, Siemieniak DR, Stark KR, Gruppo R, Sarode R, Shurin SB, Chandrasekaran V, Stabler SP, Sabio H, Bouhassira EE, Upshaw JD Jr, Ginsburg D, Tsai HM. Mutations in a member of the ADAMTS gene family cause thrombotic thrombocytopenic purpura. Nature. 2001 Oct 4;413(6855):488-94. PMID:11586351 doi:10.1038/35097008
- ↑ Kokame K, Matsumoto M, Soejima K, Yagi H, Ishizashi H, Funato M, Tamai H, Konno M, Kamide K, Kawano Y, Miyata T, Fujimura Y. Mutations and common polymorphisms in ADAMTS13 gene responsible for von Willebrand factor-cleaving protease activity. Proc Natl Acad Sci U S A. 2002 Sep 3;99(18):11902-7. Epub 2002 Aug 14. PMID:12181489 doi:10.1073/pnas.172277399
- ↑ Schneppenheim R, Budde U, Oyen F, Angerhaus D, Aumann V, Drewke E, Hassenpflug W, Haberle J, Kentouche K, Kohne E, Kurnik K, Mueller-Wiefel D, Obser T, Santer R, Sykora KW. von Willebrand factor cleaving protease and ADAMTS13 mutations in childhood TTP. Blood. 2003 Mar 1;101(5):1845-50. Epub 2002 Oct 17. PMID:12393505 doi:10.1182/blood-2002-08-2399
- ↑ Antoine G, Zimmermann K, Plaimauer B, Grillowitzer M, Studt JD, Lammle B, Scheiflinger F. ADAMTS13 gene defects in two brothers with constitutional thrombotic thrombocytopenic purpura and normalization of von Willebrand factor-cleaving protease activity by recombinant human ADAMTS13. Br J Haematol. 2003 Mar;120(5):821-4. PMID:12614216
- ↑ Assink K, Schiphorst R, Allford S, Karpman D, Etzioni A, Brichard B, van de Kar N, Monnens L, van den Heuvel L. Mutation analysis and clinical implications of von Willebrand factor-cleaving protease deficiency. Kidney Int. 2003 Jun;63(6):1995-9. PMID:12753286 doi:10.1046/j.1523-1755.63.6s.1.x
- ↑ Pimanda JE, Maekawa A, Wind T, Paxton J, Chesterman CN, Hogg PJ. Congenital thrombotic thrombocytopenic purpura in association with a mutation in the second CUB domain of ADAMTS13. Blood. 2004 Jan 15;103(2):627-9. Epub 2003 Sep 25. PMID:14512317 doi:10.1182/blood-2003-04-1346
- ↑ Matsumoto M, Kokame K, Soejima K, Miura M, Hayashi S, Fujii Y, Iwai A, Ito E, Tsuji Y, Takeda-Shitaka M, Iwadate M, Umeyama H, Yagi H, Ishizashi H, Banno F, Nakagaki T, Miyata T, Fujimura Y. Molecular characterization of ADAMTS13 gene mutations in Japanese patients with Upshaw-Schulman syndrome. Blood. 2004 Feb 15;103(4):1305-10. Epub 2003 Oct 16. PMID:14563640 doi:10.1182/blood-2003-06-1796
- ↑ Uchida T, Wada H, Mizutani M, Iwashita M, Ishihara H, Shibano T, Suzuki M, Matsubara Y, Soejima K, Matsumoto M, Fujimura Y, Ikeda Y, Murata M. Identification of novel mutations in ADAMTS13 in an adult patient with congenital thrombotic thrombocytopenic purpura. Blood. 2004 Oct 1;104(7):2081-3. Epub 2004 May 4. PMID:15126318 doi:10.1182/blood-2004-02-0715
- ↑ Veyradier A, Lavergne JM, Ribba AS, Obert B, Loirat C, Meyer D, Girma JP. Ten candidate ADAMTS13 mutations in six French families with congenital thrombotic thrombocytopenic purpura (Upshaw-Schulman syndrome). J Thromb Haemost. 2004 Mar;2(3):424-9. PMID:15009458
- ↑ Licht C, Stapenhorst L, Simon T, Budde U, Schneppenheim R, Hoppe B. Two novel ADAMTS13 gene mutations in thrombotic thrombocytopenic purpura/hemolytic-uremic syndrome (TTP/HUS). Kidney Int. 2004 Sep;66(3):955-8. PMID:15327386 doi:10.1111/j.1523-1755.2004.00841.x
- ↑ Plaimauer B, Fuhrmann J, Mohr G, Wernhart W, Bruno K, Ferrari S, Konetschny C, Antoine G, Rieger M, Scheiflinger F. Modulation of ADAMTS13 secretion and specific activity by a combination of common amino acid polymorphisms and a missense mutation. Blood. 2006 Jan 1;107(1):118-25. Epub 2005 Sep 13. PMID:16160007 doi:2005-06-2482
- ↑ Peyvandi F, Lavoretano S, Palla R, Valsecchi C, Merati G, De Cristofaro R, Rossi E, Mannuccio Mannucci P. Mechanisms of the interaction between two ADAMTS13 gene mutations leading to severe deficiency of enzymatic activity. Hum Mutat. 2006 Apr;27(4):330-6. PMID:16453338 doi:10.1002/humu.20267
- ↑ Tao Z, Anthony K, Peng Y, Choi H, Nolasco L, Rice L, Moake JL, Dong JF. Novel ADAMTS-13 mutations in an adult with delayed onset thrombotic thrombocytopenic purpura. J Thromb Haemost. 2006 Sep;4(9):1931-5. Epub 2006 Jun 22. PMID:16796708 doi:10.1111/j.1538-7836.2006.02098.x
- ↑ Shibagaki Y, Matsumoto M, Kokame K, Ohba S, Miyata T, Fujimura Y, Fujita T. Novel compound heterozygote mutations (H234Q/R1206X) of the ADAMTS13 gene in an adult patient with Upshaw-Schulman syndrome showing predominant episodes of repeated acute renal failure. Nephrol Dial Transplant. 2006 May;21(5):1289-92. Epub 2006 Jan 31. PMID:16449289 doi:gfk072
- ↑ Schneppenheim R, Kremer Hovinga JA, Becker T, Budde U, Karpman D, Brockhaus W, Hrachovinova I, Korczowski B, Oyen F, Rittich S, von Rosen J, Tjonnfjord GE, Pimanda JE, Wienker TF, Lammle B. A common origin of the 4143insA ADAMTS13 mutation. Thromb Haemost. 2006 Jul;96(1):3-6. PMID:16807643 doi:10.1160/TH05-12-0817
- ↑ Donadelli R, Banterla F, Galbusera M, Capoferri C, Bucchioni S, Gastoldi S, Nosari S, Monteferrante G, Ruggeri ZM, Bresin E, Scheiflinger F, Rossi E, Martinez C, Coppo R, Remuzzi G, Noris M. In-vitro and in-vivo consequences of mutations in the von Willebrand factor cleaving protease ADAMTS13 in thrombotic thrombocytopenic purpura. Thromb Haemost. 2006 Oct;96(4):454-64. PMID:17003922
- ↑ Meyer SC, Jeddi R, Meddeb B, Gouider E, Lammle B, Kremer Hovinga JA. A first case of congenital TTP on the African continent due to a new homozygous mutation in the catalytic domain of ADAMTS13. Ann Hematol. 2008 Aug;87(8):663-6. doi: 10.1007/s00277-008-0496-6. Epub 2008 Apr , 29. PMID:18443791 doi:10.1007/s00277-008-0496-6
- ↑ Fujimura Y, Matsumoto M, Kokame K, Isonishi A, Soejima K, Akiyama N, Tomiyama J, Natori K, Kuranishi Y, Imamura Y, Inoue N, Higasa S, Seike M, Kozuka T, Hara M, Wada H, Murata M, Ikeda Y, Miyata T, George JN. Pregnancy-induced thrombocytopenia and TTP, and the risk of fetal death, in Upshaw-Schulman syndrome: a series of 15 pregnancies in 9 genotyped patients. Br J Haematol. 2009 Mar;144(5):742-54. doi: 10.1111/j.1365-2141.2008.07515.x., Epub 2008 Nov 26. PMID:19055667 doi:10.1111/j.1365-2141.2008.07515.x
- ↑ Palla R, Lavoretano S, Lombardi R, Garagiola I, Karimi M, Afrasiabi A, Ramzi M, De Cristofaro R, Peyvandi F. The first deletion mutation in the TSP1-6 repeat domain of ADAMTS13 in a family with inherited thrombotic thrombocytopenic purpura. Haematologica. 2009 Feb;94(2):289-93. doi: 10.3324/haematol.13524. Epub 2008 Dec , 30. PMID:19116307 doi:10.3324/haematol.13524
- ↑ Lee SH, Park JH, Park SK, Lee EH, Choi JI, Visentin GP, Park TS, Oh SH, Kim SR. A novel homozygous missense ADAMTS13 mutation Y658C in a patient with recurrent thrombotic thrombocytopenic purpura. Ann Clin Lab Sci. 2011 Summer;41(3):273-6. PMID:22075512
- ↑ Kim HJ, Xu Y, Petri A, Vanhoorelbeke K, Crawley JTB, Emsley J. Crystal structure of ADAMTS13 CUB domains reveals their role in global latency. Sci Adv. 2021 Apr 16;7(16):eabg4403. PMID:33863735 doi:10.1126/sciadv.abg4403
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