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Visualizing Functional Structural Dynamics of Membrane Protein Transporters

Objective

Membrane protein transporters catalyze fundamental physiological processes in all kingdoms of life. A schematic view of membrane transport is emerging from a growing number of crystal structures. However, several fundamental features of membrane protein transport are still evasive, such as how the protein transition between states, what triggers these structural rearrangements, and how the release of energy is coupled to the transport event. The proposed research will build an interdisciplinary platform, which uses molecular biology, biophysical and computational techniques, to characterize membrane protein transport over the full spatio-temporal scale. Molecular dynamics (MD) simulations will capture high-resolution dynamics on the nano-to-microsecond timescale, which will identify communicative salt-bridge/H-bond networks, putative transport pathways, and the energetics involved in substrate transport. Predictions from the simulations will be verified by in vitro characterization of mutagenic phenotypes. Time-resolved wide-angle X-ray scattering (TR-WAXS) will monitor the micro-to-millisecond, large-scale structural rearrangements, which are out of reach for the MD simulations. The proposed platform for characterization of membrane protein transporters will be developed using a copper-transporting P-type ATPase (CopA) as the initial model system. The P-type ATPase family is divided into types I-V, depending on the transported substrate. CopA is the first crystal structure from the type-I ATPases, making it a particularly exciting model system. The applicants’ preliminary molecular dynamics (MD) simulations and the CopA transmembrane architecture strongly indicate a unique mode of transport in type-I ATPases. Hence, by means of visualization of copper transport, this proposal enables the development of an interdisciplinary European platform for multifaceted characterization of membrane transport that will be extendable to a range of membrane protein targets.

Field of science

  • /natural sciences/biological sciences/molecular biology
  • /social sciences/social and economic geography/transport

Call for proposal

FP7-PEOPLE-2013-CIG
See other projects for this call

Funding Scheme

MC-CIG - Support for training and career development of researcher (CIG)

Coordinator

KUNGLIGA TEKNISKA HOEGSKOLAN
Address
Brinellvagen 8
100 44 Stockholm
Sweden
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 100 000
Administrative Contact
Monica Thorén (Mrs.)