PDBsum entry 5eom

Transferase

PDB id: 5eom

Contents

Protein chains

(+ 3 more) 349 a.a.

286 a.a.

Ligands

CIT ×10

TMO ×4

CTP ×10

Waters ×262

PDB id:

5eom

Name:

Transferase

Title:

Structure of full-length human mab21l1 with bound ctp

Structure:

Protein mab-21-like 1. Chain: a, b, d, e, f, g, h, i, j, c. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: mab21l1, cagr1, nbla00126. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

2.55Å R-factor: 0.200 R-free: 0.227

Authors:

C.C.De Oliveira Mann,G.Witte,K.-P.Hopfner

Key ref:

C.C.de Oliveira Mann et al. (2016). Structural and biochemical characterization of the cell fate determining nucleotidyltransferase fold protein MAB21L1. Sci Rep, 6, 27498. PubMed id: 27271801 DOI: 10.1038/srep27498

Date:

10-Nov-15 Release date: 01-Jun-16

Protein chains

Q13394  (MB211_HUMAN) -  Putative nucleotidyltransferase MAB21L1 from Homo sapiens

Seq: 359 a.a.

Struc: 349 a.a.*

Protein chain

Q13394  (MB211_HUMAN) -  Putative nucleotidyltransferase MAB21L1 from Homo sapiens

Seq: 359 a.a.

Struc: 286 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

Enzyme reactions

• Enzyme class: Chains A, B, D, E, F, G, H, I, J, C: E.C.2.7.7.- - ?????

DOI no: 10.1038/srep27498

Sci Rep 6:27498 (2016)

PubMed id: 27271801

Structural and biochemical characterization of the cell fate determining nucleotidyltransferase fold protein MAB21L1.

C.C.de Oliveira Mann, R.Kiefersauer, G.Witte, K.P.Hopfner.

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.