4htp: Difference between revisions

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-{{STRUCTURE_4htp|  PDB=4htp  |  SCENE=  }}
-===Crystal structure of the DBD domain of human DNA ligase IV bound to Artemis peptide===
-{{ABSTRACT_PUBMED_23219551}}
-==Disease==
+==Crystal structure of the DBD domain of human DNA ligase IV bound to Artemis peptide==
-[[http://www.uniprot.org/uniprot/DNLI4_HUMAN DNLI4_HUMAN]] Defects in LIG4 are the cause of LIG4 syndrome (LIG4S) [MIM:[http://omim.org/entry/606593 606593]]. This disease is characterized by immunodeficiency and developmental and growth delay. Patients display unusual facial features, microcephaly, growth and/or developmental delay, pancytopenia, and various skin abnormalities.<ref>PMID:11779494</ref>  Defects in LIG4 are a cause of severe combined immunodeficiency autosomal recessive T-cell-negative/B-cell-negative/NK-cell-positive with sensitivity to ionizing radiation (RSSCID) [MIM:[http://omim.org/entry/602450 602450]]. SCID refers to a genetically and clinically heterogeneous group of rare congenital disorders characterized by impairment of both humoral and cell-mediated immunity, leukopenia, and low or absent antibody levels. Patients with SCID present in infancy with recurrent, persistent infections by opportunistic organisms. The common characteristic of all types of SCID is absence of T-cell-mediated cellular immunity due to a defect in T-cell development. Individuals affected by RS-SCID show defects in the DNA repair machinery necessary for coding joint formation and the completion of V(D)J recombination. A subset of cells from such patients show increased radiosensitivity.
+<StructureSection load='4htp' size='340' side='right'caption='[[4htp]], [[Resolution|resolution]] 2.25&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[4htp]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4HTP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4HTP FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.2502&#8491;</td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4htp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4htp OCA], [https://pdbe.org/4htp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4htp RCSB], [https://www.ebi.ac.uk/pdbsum/4htp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4htp ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[https://www.uniprot.org/uniprot/DNLI4_HUMAN DNLI4_HUMAN] Defects in LIG4 are the cause of LIG4 syndrome (LIG4S) [MIM:[https://omim.org/entry/606593 606593]. This disease is characterized by immunodeficiency and developmental and growth delay. Patients display unusual facial features, microcephaly, growth and/or developmental delay, pancytopenia, and various skin abnormalities.<ref>PMID:11779494</ref>   Defects in LIG4 are a cause of severe combined immunodeficiency autosomal recessive T-cell-negative/B-cell-negative/NK-cell-positive with sensitivity to ionizing radiation (RSSCID) [MIM:[https://omim.org/entry/602450 602450]. SCID refers to a genetically and clinically heterogeneous group of rare congenital disorders characterized by impairment of both humoral and cell-mediated immunity, leukopenia, and low or absent antibody levels. Patients with SCID present in infancy with recurrent, persistent infections by opportunistic organisms. The common characteristic of all types of SCID is absence of T-cell-mediated cellular immunity due to a defect in T-cell development. Individuals affected by RS-SCID show defects in the DNA repair machinery necessary for coding joint formation and the completion of V(D)J recombination. A subset of cells from such patients show increased radiosensitivity.
+== Function ==
+[https://www.uniprot.org/uniprot/DNLI4_HUMAN DNLI4_HUMAN] Efficiently joins single-strand breaks in a double-stranded polydeoxynucleotide in an ATP-dependent reaction. Involved in DNA non-homologous end joining (NHEJ) required for double-strand break repair and V(D)J recombination. The LIG4-XRCC4 complex is responsible for the NHEJ ligation step, and XRCC4 enhances the joining activity of LIG4. Binding of the LIG4-XRCC4 complex to DNA ends is dependent on the assembly of the DNA-dependent protein kinase complex DNA-PK to these DNA ends.<ref>PMID:9809069</ref> <ref>PMID:10854421</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+DNA ligase IV (LigIV) and Artemis are central components of the nonhomologous end-joining (NHEJ) machinery that is required for V(D)J recombination and the maintenance of genomic integrity in mammalian cells. We report here crystal structures of the LigIV DNA binding domain (DBD) in both its apo form and in complex with a peptide derived from the Artemis C-terminal region. We show that LigIV interacts with Artemis through an extended hydrophobic surface. In particular, we find that the helix alpha2 in LigIV-DBD is longer than in other mammalian ligases and presents residues that specifically interact with the Artemis peptide, which adopts a partially helical conformation on binding. Mutations of key residues on the LigIV-DBD hydrophobic surface abolish the interaction. Together, our results provide structural insights into the specificity of the LigIV-Artemis interaction and how the enzymatic activities of the two proteins may be coordinated during NHEJ.
-==Function==
+Structural Basis of DNA Ligase IV-Artemis Interaction in Nonhomologous End-Joining.,De Ioannes P, Malu S, Cortes P, Aggarwal AK Cell Rep. 2012 Dec 27;2(6):1505-12. doi: 10.1016/j.celrep.2012.11.004. Epub 2012 , Dec 7. PMID:23219551<ref>PMID:23219551</ref>
-[[http://www.uniprot.org/uniprot/DNLI4_HUMAN DNLI4_HUMAN]] Efficiently joins single-strand breaks in a double-stranded polydeoxynucleotide in an ATP-dependent reaction. Involved in DNA non-homologous end joining (NHEJ) required for double-strand break repair and V(D)J recombination. The LIG4-XRCC4 complex is responsible for the NHEJ ligation step, and XRCC4 enhances the joining activity of LIG4. Binding of the LIG4-XRCC4 complex to DNA ends is dependent on the assembly of the DNA-dependent protein kinase complex DNA-PK to these DNA ends.<ref>PMID:9809069</ref><ref>PMID:10854421</ref>
-==About this Structure==
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[4htp]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4HTP OCA].
+</div>
+<div class="pdbe-citations 4htp" style="background-color:#fffaf0;"></div>
 ==See Also==
-*[[DNA ligase|DNA ligase]]
+*[[DNA ligase 3D structures|DNA ligase 3D structures]]
+== References ==
-==Reference==
+<references/>
-<references group="xtra"/><references/>
+__TOC__
+</StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Aggarwal, A K.]]
+[[Category: Large Structures]]
-[[Category: Ioannes, P E.De.]]
+[[Category: Aggarwal AK]]
-[[Category: Artemi]]
+[[Category: De Ioannes PE]]
-[[Category: Dna]]
-[[Category: Dna binding domain]]
-[[Category: Helical domain]]
-[[Category: Ligase-hydrolase complex]]