7KIU

Structure of recombinant human DNase1L3 in complex with Mg2+

Summary for 7KIU

• Entry DOI: 10.2210/pdb7kiu/pdb
• Descriptor: Deoxyribonuclease gamma, MAGNESIUM ION (3 entities in total)
• Functional Keywords: nuclease, dna hydrolase, apoptosis, lupus, systemic lupus erythematosus, sle, dna clearance, metal ion nuclease, net clearance, hydrolase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 4
• Total formula weight: 131381.21

Authors

McCord, J.J.,Keyel, P.A.,Sutton, R.B. (deposition date: 2020-10-24, release date: 2021-12-01, Last modification date: 2024-11-06)

Primary citation

McCord, J.J.,Engavale, M.,Masoumzadeh, E.,Villarreal, J.,Mapp, B.,Latham, M.P.,Keyel, P.A.,Sutton, R.B.
Structural features of Dnase1L3 responsible for serum antigen clearance.
Commun Biol, 5:825-825, 2022

PubMed Abstract: Autoimmunity develops when extracellular DNA released from dying cells is not cleared from serum. While serum DNA is primarily digested by Dnase1 and Dnase1L3, Dnase1 cannot rescue autoimmunity arising from Dnase1L3 deficiencies. Dnase1L3 uniquely degrades antigenic forms of cell-free DNA, including DNA complexed with lipids and proteins. The distinct activity of Dnase1L3 relies on its unique C-terminal Domain (CTD), but the mechanism is unknown. We used multiple biophysical techniques and functional assays to study the interplay between the core catalytic domain and the CTD. While the core domain resembles Dnase1, there are key structural differences between the two enzymes. First, Dnase1L3 is not inhibited by actin due to multiple differences in the actin recognition site. Second, the CTD augments the ability of the core to bind DNA, thereby facilitating the degradation of complexed DNA. Together, these structural insights will inform the development of Dnase1L3-based therapies for autoimmunity.

PubMed: 35974043
DOI: 10.1038/s42003-022-03755-5

Experimental method

X-RAY DIFFRACTION (2.22 Å)