Structural and functional characterization of the brain-specific dynamin superfamily member RNF112
Abstract
Most members of the dynamin superfamily of large guanosine triphophatases (GTPases) have an ability to remodel membranes in response to guanosine triphosphate (GTP) hydrolysis. Ring Finger Protein 112 (RNF112) (ZNF179/neurolastin) is a recently identified brain-specific dynamin-like protein possessing a really interesting new gene (RING) finger domain. Despite its essential role as an E3 ligase in neuron development, the architecture of RNF112 and the exact role of its GTPase activity remain unknown. Here, we determined the crystal structure of truncated RNF112 (RNF112 T ) containing a GTPase domain (GD) and three-helical middle domain (MD) at different nucleotide-loading states. In the nucleotide-free (apo) state, the monomeric RNF112 T remained in a unique self-restraint conformation characterized by docking of the proximal end of the MD to a groove in the GD. At the transition state of GTP hydrolysis, the MD was released from the GD and stretched aside to form an intertwined RNF112 T homodimer. Engineered RNF112 equipped with the C-terminal elements of ATL1 or the two transmembrane domains of yeast Sac1p relocated to the endoplasmic reticulum and was capable of mediating membrane remodeling. Taken together, our results offer necessary understandings of RNF112 as a dynamin-like large GTPase in its cellular function and provide insights into the functional mechanisms of dynamin superfamily proteins.
Article Details
Journal Info
Proceedings of the National Academy of Sciences
National Academy of Sciences
Authors (17)
Ya-Ting Zhong
Guangdong Provincial Clinical Research Center for Cancer, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center
Li-Li Huang
Guangdong Provincial Clinical Research Center for Cancer, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center
Kangning Li
State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Frontiers Science Center for Cell Responses, Nankai University
Bingke Yang
State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Frontiers Science Center for Cell Responses, Nankai University
Xueting Ye
Department of Chemistry and Research Center for Chemical Biology and Omics Analysis, College of Science, Southern University of Science and Technology
Hao-Ran Zhong
Guangdong Provincial Clinical Research Center for Cancer, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center
Bing Yu
College of Chemistry and Materials Science, Guangdong Provincial Key Laboratory of Supramolecular Coordination Chemistry
Menghan Ma
State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Frontiers Science Center for Cell Responses, Nankai University
Yuerong Yuan
College of Life Sciences, Nankai University
Yang Meng
Department of Chemistry
Runfeng Pan
College of Life Sciences, Nankai University
Haiqing Zhang
College of Life Sciences, Nankai University
Lijun Shi
State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Frontiers Science Center for Cell Responses, Nankai University
Yunyun Wang
State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Frontiers Science Center for Cell Responses, Nankai University
Ruijun Tian
Taizhou Research Institute
Song Gao
Xin Bian
State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Frontiers Science Center for Cell Responses, Nankai University