Research report 2003 - Max Planck Institute of Molecular Physiology

Structural and mechanistic aspects of intracellular vesicular transport regulation

Alexandrov, Kirill; Durek, Thomas; Goody, Roger S.; Niculae, Anca; Pylypenko, Olena; Rak, Alexey; Schlichting, Ilme; Reents, Reinhard (Abt. 4); Waldmann, Herbert (Abt. 4); Watzke, Anja (Abt. 4)

Physikalische Biochemie (Prof. Dr. Roger Goody)
MPI für molekulare Physiologie, Dortmund

The integrity of eukaryotic cells depends on their ability to maintain an array of dynamic membrane bound intracellular structures such as endosomes, lysosomes, Golgi apparatus etc. These organelles communicate with each other and the cellular environment via shuttling transport vesicles in a process known as intracellular vesicular transport. This process is governed by GTPases of the Rab family that function as molecular switches controlling events of vesicular transport, docking and fusion. In order to perform their function RabGTPases have to associate with cell membranes via covalently attached lipid moieties. This modification, which is conferred posttranslationally by the multisubunit enzyme Rab geranylgeranyl transferase (RabGGTase) enables Rab proteins to interact with membranes and other regulatory proteins such as Rab GDP dissociation inhibitor (RabGDI). Mutations interfering with either Rab prenylation or Rab:GDI interaction are known to lead to a number of pathologic conditions in humans. Scientists from MPI for Molecular Physiology have used a combination of protein semi-synthesis, kinetic analysis and X-ray crystallography to elucidate the structure and function of RabGGTase subunits and RabGDI in complex with Rab GTPases. Based on these data they provide a mechanistic model for human choroideremia disease and non-syndromic mental retardation.

For the full text, see the German version.

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