5EOM

Structure of full-length human MAB21L1 with bound CTP

Summary for 5EOM

• Entry DOI: 10.2210/pdb5eom/pdb
• Related: 5EOG
• Descriptor: Protein mab-21-like 1, CITRIC ACID, trimethylamine oxide, ... (5 entities in total)
• Functional Keywords: nucleotidyltransferase fold protein, transferase
• Biological source: Homo sapiens (Human)
• Cellular location: Nucleus : Q13394
• Total number of polymer chains: 10
• Total formula weight: 419649.41

Authors

de Oliveira Mann, C.C.,Witte, G.,Hopfner, K.-P. (deposition date: 2015-11-10, release date: 2016-06-01, Last modification date: 2024-05-01)

Primary citation

de Oliveira Mann, C.C.,Kiefersauer, R.,Witte, G.,Hopfner, K.P.
Structural and biochemical characterization of the cell fate determining nucleotidyltransferase fold protein MAB21L1.
Sci Rep, 6:27498-27498, 2016

PubMed Abstract: 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.

PubMed: 27271801
DOI: 10.1038/srep27498

Experimental method

X-RAY DIFFRACTION (2.55 Å)