A.M. dos Santos Duarte: “Molecular behaviour of a proton channels in membranes”

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8 Oct 2007 13:30
Unit: Wageningen University
Location: Aula, building 362, Gen. Foulkesweg 1, Wageningen
Organisation: Wageningen University
Promotor: prof.dr. H. Van Amerongen (Bio-physics)
Co Promotor: Dr. M.A. Hemminga, Dr.ir. C.P.M. van Mierlo

 The World Health Organization regards the bone disease osteoporosis as one of the world’s most important health problems. The objective of this project, as part of a major EU consortium, was the design of new drugs to target this disease. We focused on a detailed analysis of the molecular structure and functional mechanism of the membrane protein vacuolar ATPase. This enzyme plays an important role in osteoporosis, because its malfunction leads to bone tissue acidification resulting in bone demineralisation (i.e., the bone becomes fragile and susceptible to fractures). I focused on an important domain of this enzyme that is known to control the acidification of the bone tissue. Making use of the most advanced biophysical techniques available, I experimentally determined for the first time the atomic structure of this domain. Furthermore, this information allows us to propose a possible mechanism for the proton translocation and a particular molecular site that can act as a target for new drugs.

Title thesis : “Structure and dynamics of an essential transmembrane segment of the proton translocation channel of V-ATPase”
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