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PDBsum entry 5eom
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Contents |
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(+ 3 more)
349 a.a.
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286 a.a.
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References listed in PDB file
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Key reference
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Title
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Structural and biochemical characterization of the cell fate determining nucleotidyltransferase fold protein mab21l1.
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Authors
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C.C.De oliveira mann,
R.Kiefersauer,
G.Witte,
K.P.Hopfner.
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Ref.
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Sci Rep, 2016,
6,
27498.
[DOI no: ]
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PubMed id
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Abstract
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The exceptionally conserved metazoan MAB21 proteins are implicated in cell fate
decisions and share considerable sequence homology with the cyclic GMP-AMP
synthase. cGAS is the major innate immune sensor for cytosolic DNA and produces
the second messenger 2'-5', 3'-5' cyclic GMP-AMP. Little is known about the
structure and biochemical function of other proteins of the cGAS-MAB21
subfamily, such as MAB21L1, MAB21L2 and MAB21L3. We have determined the crystal
structure of human full-length MAB21L1. Our analysis reveals high structural
conservation between MAB21L1 and cGAS but also uncovers important differences.
Although monomeric in solution, MAB21L1 forms a highly symmetric
double-pentameric oligomer in the crystal, raising the possibility that
oligomerization could be a feature of MAB21L1. In the crystal, MAB21L1 is in an
inactive conformation requiring a conformational change - similar to cGAS - to
develop any nucleotidyltransferase activity. Co-crystallization with NTP
identified a putative ligand binding site of MAB21 proteins that corresponds to
the DNA binding site of cGAS. Finally, we offer a structure-based explanation
for the effects of MAB21L2 mutations in patients with eye malformations. The
underlying residues participate in fold-stabilizing interaction networks and
mutations destabilize the protein. In summary, we provide a first structural
framework for MAB21 proteins.
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