4WOY

Crystal structure and functional analysis of MiD49, a receptor for the mitochondrial fission protein Drp1

Summary for 4WOY

• Entry DOI: 10.2210/pdb4woy/pdb
• Related: 4WP0
• Descriptor: Mitochondrial dynamics protein MID49 (2 entities in total)
• Functional Keywords: mid49, mitochondrial fission, nucleotidyl transferase, transferase
• Biological source: Mus musculus (Mouse)
• Cellular location: Mitochondrion outer membrane ; Single-pass membrane protein : Q5NCS9
• Total number of polymer chains: 2
• Total formula weight: 73160.14

Authors

Loson, O.C.,Meng, S.,Ngo, H.B.,Liu, R.,Kaiser, J.T.,Chan, D.C. (deposition date: 2014-10-17, release date: 2015-01-28, Last modification date: 2023-12-27)

Primary citation

Loson, O.C.,Meng, S.,Ngo, H.,Liu, R.,Kaiser, J.T.,Chan, D.C.
Crystal structure and functional analysis of MiD49, a receptor for the mitochondrial fission protein Drp1.
Protein Sci., 24:386-394, 2015

PubMed Abstract: Mitochondrial fission requires recruitment of dynamin-related protein 1 (Drp1) to the mitochondrial surface, where assembly leads to activation of its GTP-dependent scission function. MiD49 and MiD51 are two receptors on the mitochondrial outer membrane that can recruit Drp1 to facilitate mitochondrial fission. Structural studies indicated that MiD51 has a variant nucleotidyl transferase fold that binds an ADP co-factor essential for activation of Drp1 function. MiD49 shares sequence homology with MiD51 and regulates Drp1 function. However, it is unknown if MiD49 binds an analogous co-factor. Because MiD49 does not readily crystallize, we used structural predictions and biochemical screening to identify a surface entropy reduction mutant that facilitated crystallization. Using molecular replacement, we determined the atomic structure of MiD49 to 2.4 Å. Like MiD51, MiD49 contains a nucleotidyl transferase domain; however, the electron density provides no evidence for a small-molecule ligand. Structural changes in the putative nucleotide-binding pocket make MiD49 incompatible with an extended ligand like ADP, and critical nucleotide-binding residues found in MiD51 are not conserved. MiD49 contains a surface loop that physically interacts with Drp1 and is necessary for Drp1 recruitment to the mitochondrial surface. Our results suggest a structural basis for the differential regulation of MiD51- versus MiD49-mediated fission.

PubMed: 25581164
DOI: 10.1002/pro.2629

Experimental method

X-RAY DIFFRACTION (2.4 Å)