دورية أكاديمية
Crystal structure of the Mre11-Rad50-ATPγS complex: understanding the interplay between Mre11 and Rad50.
| العنوان: | Crystal structure of the Mre11-Rad50-ATPγS complex: understanding the interplay between Mre11 and Rad50. |
|---|---|
| المؤلفون: | Lim HS; Department of Life Science, Pohang University of Science and Technology, Pohang, South Korea., Kim JS, Park YB, Gwon GH, Cho Y |
| المصدر: | Genes & development [Genes Dev] 2011 May 15; Vol. 25 (10), pp. 1091-104. Date of Electronic Publication: 2011 Apr 21. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Cold Spring Harbor Laboratory Press Country of Publication: United States NLM ID: 8711660 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1549-5477 (Electronic) Linking ISSN: 08909369 NLM ISO Abbreviation: Genes Dev Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Cold Spring Harbor, NY : Cold Spring Harbor Laboratory Press Original Publication: [Cold Spring Harbor, N.Y.] : Cold Spring Harbor Laboratory in association with the Genetical Society of Great Britain, [c1987- |
| مواضيع طبية MeSH: | Models, Molecular*, Adenosine Triphosphate/*analogs & derivatives , Archaeal Proteins/*chemistry , Endodeoxyribonucleases/*chemistry , Exodeoxyribonucleases/*chemistry , Methanococcus/*chemistry , Methanococcus/*metabolism, Adenosine Triphosphate/chemistry ; Adenosine Triphosphate/metabolism ; Amino Acid Motifs ; Archaeal Proteins/metabolism ; Binding Sites ; Endodeoxyribonucleases/metabolism ; Exodeoxyribonucleases/metabolism ; Gene Expression Regulation, Archaeal ; Hydrolysis ; Methanococcus/enzymology ; Methanococcus/genetics ; Protein Binding ; Protein Structure, Quaternary ; Protein Structure, Tertiary |
| مستخلص: | Communication between Mre11 and Rad50 in the MR complex is critical for the sensing, damage signaling, and repair of DNA double-strand breaks. To understand the basis for interregulation between Mre11 and Rad50, we determined the crystal structure of the Mre11-Rad50-ATPγS complex. Mre11 brings the two Rad50 molecules into close proximity and promotes ATPase activity by (1) holding the coiled-coil arm of Rad50 through its C-terminal domain, (2) stabilizing the signature motif and P loop of Rad50 via its capping domain, and (3) forming a dimer through the nuclease domain. ATP-bound Rad50 negatively regulates the nuclease activity of Mre11 by blocking the active site of Mre11. Hydrolysis of ATP disengages Rad50 molecules, and, concomitantly, the flexible linker that connects the C-terminal domain and the capping domain of Mre11 undergoes substantial conformational change to relocate Rad50 and unmask the active site of Mre11. Our structural and biochemical data provide insights into understanding the interplay between Mre11 and Rad50 to facilitate efficient DNA damage repair. |
| References: | Proc Natl Acad Sci U S A. 1999 Jun 22;96(13):7376-81. (PMID: 10377422) EMBO Rep. 2002 Mar;3(3):248-54. (PMID: 11850399) J Mol Biol. 2007 Sep 28;372(4):864-882. (PMID: 17698079) Acta Crystallogr D Biol Crystallogr. 1998 Sep 1;54(Pt 5):905-21. (PMID: 9757107) Curr Biol. 2004 Oct 5;14(19):1778-82. (PMID: 15458651) EMBO J. 2006 Nov 29;25(23):5527-38. (PMID: 17082765) Science. 2005 Apr 22;308(5721):551-4. (PMID: 15790808) Cell. 2008 Oct 3;135(1):97-109. (PMID: 18854158) Mol Oncol. 2008 Dec;2(4):296-316. (PMID: 19383352) Nat Struct Mol Biol. 2009 Aug;16(8):819-24. (PMID: 19633668) J Biol Chem. 2001 Sep 21;276(38):35458-64. (PMID: 11454871) J Mol Biol. 2004 Jun 11;339(4):937-49. (PMID: 15165861) J Biol Chem. 2005 Jan 28;280(4):2620-7. (PMID: 15546877) EMBO J. 2008 Feb 20;27(4):581-8. (PMID: 18285819) EMBO J. 2004 Jul 7;23(13):2664-73. (PMID: 15175656) Cell. 2009 Jan 9;136(1):85-96. (PMID: 19135891) Cell. 2001 May 18;105(4):473-85. (PMID: 11371344) Mol Cell. 1998 Jun;1(7):969-79. (PMID: 9651580) Nat Genet. 2001 Mar;27(3):247-54. (PMID: 11242102) Nat Rev Mol Cell Biol. 2002 May;3(5):317-27. (PMID: 11988766) Nucleic Acids Res. 1999 Mar 1;27(5):1223-42. (PMID: 9973609) Cell. 1998 May 1;93(3):477-86. (PMID: 9590181) Cell. 2000 Jun 23;101(7):789-800. (PMID: 10892749) Curr Biol. 2004 Dec 14;14(23):2107-12. (PMID: 15589152) Nature. 2005 Sep 15;437(7057):440-3. (PMID: 16163361) Methods Enzymol. 1997;276:307-26. (PMID: 27754618) Proc Natl Acad Sci U S A. 1998 Jul 7;95(14):7969-74. (PMID: 9653124) EMBO J. 2007 Feb 7;26(3):867-77. (PMID: 17255941) J Mol Biol. 2004 Jan 23;335(4):937-51. (PMID: 14698290) Nature. 2009 Oct 22;461(7267):1071-8. (PMID: 19847258) J Biol Chem. 2011 Jan 28;286(4):2382-92. (PMID: 21081488) Cancer Res. 2004 May 1;64(9):2998-3001. (PMID: 15126332) Mol Cell. 2001 Nov;8(5):1105-15. (PMID: 11741545) Mol Cell. 2001 Nov;8(5):1129-35. (PMID: 11741547) Nucleic Acids Res. 1997 Aug 1;25(15):2985-91. (PMID: 9224597) Cancer Res. 2003 Nov 1;63(21):7263-9. (PMID: 14612522) J Biol Chem. 1998 Aug 21;273(34):21447-50. (PMID: 9705271) Curr Biol. 2001 Jan 23;11(2):105-9. (PMID: 11231126) Curr Biol. 2006 Oct 24;16(20):1998-2008. (PMID: 17055978) J Mol Biol. 2010 Apr 2;397(3):647-63. (PMID: 20122942) Curr Biol. 2005 Apr 12;15(7):R265-75. (PMID: 15823530) Acta Crystallogr D Biol Crystallogr. 2004 Dec;60(Pt 12 Pt 1):2126-32. (PMID: 15572765) J Biol Chem. 2003 Dec 5;278(49):48957-64. (PMID: 14522986) DNA Repair (Amst). 2004 Aug-Sep;3(8-9):1219-25. (PMID: 15279810) Acta Crystallogr D Biol Crystallogr. 2010 Feb;66(Pt 2):213-21. (PMID: 20124702) Genes Dev. 1999 May 15;13(10):1276-88. (PMID: 10346816) Cell. 2008 Oct 3;135(1):85-96. (PMID: 18854157) J Biol Chem. 2001 Oct 5;276(40):37027-33. (PMID: 11470800) J Bacteriol. 2000 Nov;182(21):6036-41. (PMID: 11029422) |
| المشرفين على المادة: | 0 (Archaeal Proteins) 35094-46-3 (adenosine 5'-O-(3-thiotriphosphate)) 8L70Q75FXE (Adenosine Triphosphate) EC 3.1.- (Endodeoxyribonucleases) EC 3.1.- (Exodeoxyribonucleases) EC 3.1.- (Mre11 protein, archaeal) EC 3.1.- (Rad50 protein, archaeal) |
| تواريخ الأحداث: | Date Created: 20110423 Date Completed: 20110706 Latest Revision: 20211020 |
| رمز التحديث: | 20231215 |
| مُعرف محوري في PubMed: | PMC3093124 |
| DOI: | 10.1101/gad.2037811 |
| PMID: | 21511873 |
| قاعدة البيانات: | MEDLINE |
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