5eog | pdb_00005eog
Structure of full-length human MAB21L1
Structural highlights
FunctionMB211_HUMAN Required for several aspects of embryonic development including normal development of the eye. Publication Abstract from PubMedThe 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. Structural and biochemical characterization of the cell fate determining nucleotidyltransferase fold protein MAB21L1.,de Oliveira Mann CC, Kiefersauer R, Witte G, Hopfner KP Sci Rep. 2016 Jun 8;6:27498. doi: 10.1038/srep27498. PMID:27271801[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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