6B3Y

Crystal structure of the PH-like domain from DENND3

Summary for 6B3Y

• Entry DOI: 10.2210/pdb6b3y/pdb
• Descriptor: DENN domain-containing protein 3 (2 entities in total)
• Functional Keywords: autophagy, guanine nucleotide exchange factor, ph-like fold, transport protein
• Biological source: Mus musculus (Mouse)
• Total number of polymer chains: 2
• Total formula weight: 58483.83

Authors

Kozlov, G.,Xu, J.,Menade, M.,Beaugrand, M.,Pan, T.,McPherson, P.S.,Gehring, K. (deposition date: 2017-09-25, release date: 2018-01-24, Last modification date: 2024-03-13)

Primary citation

Xu, J.,Kozlov, G.,McPherson, P.S.,Gehring, K.
A PH-like domain of the Rab12 guanine nucleotide exchange factor DENND3 binds actin and is required for autophagy.
J. Biol. Chem., 293:4566-4574, 2018

PubMed Abstract: Rab GTPases are key regulators of membrane trafficking, and many are activated by guanine nucleotide exchange factors bearing a ifferentially xpressed in ormal and eoplastic cells (DENN) domain. By activating the small GTPase Rab12, DENN domain-containing protein 3 (DENND3) functions in autophagy. Here, we identified a structural domain (which we name PHenn) containing a pleckstrin homology subdomain that binds actin and is required for DENND3 function in autophagy. We found that a hydrophobic patch on an extended β-turn of the PHenn domain mediates an intramolecular interaction with the DENN domain of DENND3. We also show that DENND3 binds actin through a surface of positively charged residues on the PHenn domain. Substitutions that blocked either DENN or actin binding compromised the role of DENND3 in autophagy. These results provide new mechanistic insight into the structural determinants regulating DENND3 in autophagy and lay the foundation for future investigations of the DENN protein family.

PubMed: 29352104
DOI: 10.1074/jbc.RA117.001446

Experimental method

X-RAY DIFFRACTION (1.852 Å)