7d9y: Difference between revisions
New page: '''Unreleased structure''' The entry 7d9y is ON HOLD Authors: Description: Category: Unreleased Structures |
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The | ==DNA binding domain of human DNA Ligase IV mutant - A3V== | ||
<StructureSection load='7d9y' size='340' side='right'caption='[[7d9y]], [[Resolution|resolution]] 2.76Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[7d9y]] is a 1 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=7D9Y OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7D9Y 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]] 2.76Å</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=7d9y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7d9y OCA], [https://pdbe.org/7d9y PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7d9y RCSB], [https://www.ebi.ac.uk/pdbsum/7d9y PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7d9y 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 == | |||
Studies have shown that Lig4 syndrome mutations in DNA ligase IV (LigIV) are compromised in its function with residual level of double strand break ligation activity in vivo. It was speculated that Lig4 syndrome mutations adversely affect protein folding and stability. Though there are crystal structures of LigIV, there are no reports of crystal structures of Lig4 syndrome mutants and their biophysical characterization to date. Here, we have examined the conformational states, thermal stability, hydrophobicity and DNA binding efficiency of human DNA LigIV wild type and its hypomorphic mutants by far-UV circular dichroism, tyrosine and tryptophan fluorescence, and 1-anilino-8-naphthalene-sulfonate binding, dynamic light scattering, size exclusion chromatography, multi-angle light scattering and electrophoretic mobility shift assay. We show here that LigIV hypomorphic mutants have reduced DNA-binding efficiency, a shift in secondary structure content from the helical to random coil, marginal reduction in their thermal stability and increased hydrophobicity as compared to the wild-type LigIV. | |||
Hypomorphic mutations in human DNA ligase IV lead to compromised DNA binding efficiency, hydrophobicity and thermal stability.,Maddi ER, Raghavan SC, Natesh R Protein Eng Des Sel. 2021 Feb 15;34. pii: 6135054. doi: 10.1093/protein/gzab001. PMID:33586762<ref>PMID:33586762</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 7d9y" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[DNA ligase 3D structures|DNA ligase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Maddi ER]] | |||
[[Category: Natesh R]] | |||
[[Category: Raghavan SC]] | |||