|Ph.D Student||Abutbul Ionita Inbal|
|Subject||Structure-Function Studies of Proteins of the Dynamin Family|
|Department||Department of Biotechnology and Food Engineering||Supervisor||Professor Dganit Danino|
|Full Thesis text|
Proteins of the dynamin family are large GTPases found in animal, yeast and plant cells. They share high sequence homology, structural motifs, biochemical characteristics, and the ability to self-assemble into ordered structures and interact with cellular membranes. At the same time, dynamin family members are implicated in diverse fundamental cellular processes. Here we present structure-function studies of distinct highly-ordered complexes, which are customized to fit diverse cellular functions. The study focuses on three family members: dynamin, MxA, and Mgm1.
Dynamin is considered to be the prototype for proteins of the dynamin family. It is essential for many biological functions that require fission, such as endocytosis, synaptic recycling, and vesicle trafficking. Dynamin assembles into helical structures at the necks of budding vesicles, and assists the release of vesicles from the membrane upon GTP binding and hydrolysis. In-vitro dynamin wraps around liposomes and transform them into long helical tubes, with a diameter similar to that of endocytic buds. Upon GTP hydrolysis, dynamin applies force on the underlying membrane and constricts, decreasing the distance between bilayers, and facilitating fission.
Mgm1 function in mitochondrial membrane fusion and the formation and maintenance of cristae structures. The protein mechanism of action in these processes is yet to be discovered. s-Mgm1 was successfully expressed and purified only recently and to date very little work examined the protein characteristics in-vitro. Preliminary work in our lab focused on s-Mgm1-lipid interactions. We found that s-Mgm1 forms unique membrane associated structures that are novel for the dynamin family. s-Mgm1 does not tubulate single liposomes like all known dynamins. Instead, it crystallizes onto the leaflets of liposomes, then bridges the membranes of neighboring liposomes and anchors them at a fixed distance. s-Mgm1 structures of bridged liposomes strikingly resemble mitochondrial cristae structures and could be the first step towards fusion.