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Structural Studies of the Human Water Channel Protein Aquaporin 5

Anna Backmark (Institutionen för kemi- och bioteknik)
Göteborg : Chalmers University of Technology, 2008. - 31 + papers s.
[Licentiatavhandling]

Aquaporins are water channel proteins found in the membranes of all living cells. In humans, thirteen aquaporins have been identified to date. Many of them have been implicated in water imbalance disorders. Water transport through the aquaporins is regulated at several levels. Regulation by trafficking involves translocation of aquaporin containing vesicles from intracellular storage sites to the cell membrane in response to cellular stimuli and after protein phosphorylation. Protein trafficking is a universal mechanism of great importance for cellular function.

This thesis presents the X-ray structure of human aquaporin 5 (AQP5). It is the first structure of a human aquaporin with enough detail to detect structural features unique to the aquaporin homologues in man. The structure of AQP5 presents new information regarding the functional role of the putative tetrameric pore of aquaporins. Contradictory to suggestions of a transport function for this pore in other aquaporins, a lipid molecule completely occludes the pore in the centre of the AQP5 tetramer. The structure of AQP5 further provides insights into structural events that may signal the protein for trafficking. Four potential phosphorylation sites are revealed in the structure.

The structure of AQP5 was solved using two constructs, one of which included a C-terminal affinity tag (His-tag). Comparison of aquaporin structures with and without a His-tag indicated that the tag influences crystal packing. The tag was found to reduce the diffraction resolution. However, the tag introduced additional spacing and asymmetry in the crystal packing, which reduced or prevented merohedral twinning.

Nyckelord: aquaporins, aquaporin 5, X-ray crystallography, structure, trafficking, twinning



Denna post skapades 2008-10-08. Senast ändrad 2008-10-09.
CPL Pubid: 74965

 

Institutioner (Chalmers)

Institutionen för kemi- och bioteknik (2005-2014)

Ämnesområden

Strukturbiokemi

Chalmers infrastruktur

Examination

Datum: 2008-10-30
Tid: 10:00
Lokal: KC-salen, Kemigården 4, Göteborg

Ingår i serie

Licentiatuppsatser vid Institutionen för kemi- och bioteknik, Chalmers tekniska högskola 2008:15