It is appealing to speculate that TA proteins are the modern descendents of the fi rst integral membrane proteins found in the last universal common ancestor (LUCA).
Primitive membranes most probably did not come equipped with the highly conserved and extensive PCC machineries found today. Therefore spontaneous integration of polypeptides into the lipid bilayer would have been the only mechanism available. These fi rst integral membrane proteins could then have also served to enhance the integration of other proteins into the membrane. This would explain why the PCC channels discussed here all contain TA protein subunits that quite often function to stabilize the protein complexes (Table 2). The Bcl-2 proteins represent just one group of TA proteins that exploit this mechanism of instant membrane integration. By employing various mechanisms to control the availability of the C-terminal TMD for membrane insertion, they are able to generate spatial and temporal regulation of cellular localization.
Concluding remarks
Acknowledgements
Acknowledements
This work was carried out at the Institute of Biotechnology, University of Helsinki, dur-ing 2001-2006. I acknowledge the fi nancial support provided by the Research Founda-tion of the University of Helsinki, the Helsinki Graduate School in Biotechnology and Molecular Biology, and the Federation of European Biochemical Societies.
I wish to express my gratitude to my supervisor Professor Marja Makarow for her support, guidance, and encouragement. These years under her supervision have been an invaluable learning experience.
I would also like to thank my collaborators and co-authors Nica Borgese, Silvia Brambillasca, Paolo Soffi entini, Emanuela Pedrazzini, Sandra Stefanovic, Ramanujan Hegde, Urmas Arumäe, Eija Jokitalo, and Maili Jakobson. Their contributions to this work are acknowledged and I am very grateful for the opportunities these very fruitful collaborations have given me to acquire new and valuable skills. I also value the oppor-tunities these collaborations have given me to expand my scientifi c horizons.
To my thesis reviewers Docent Vesa Olkkonen and Dr Thomas Sommer, I would like to convey my gratitude for their constructive criticisms of my thesis.
My gratitude also extends to the members of my follow up group Jussi Jäntti and Urmas Arumäe. Your inputs and encouragement at our meetings have been very helpful.
I would also like to thank Leevi Kääriäinen for his help and encouragement especially this last year.
I also thank the members of the Institute of Biotechnology and its director Professor Mart Saarma for their contributions in making Viikki a wonderful place to work at. At no time have I felt alone here, as there has always been someone with whom to share my wins and losses in my continual scientifi c battles. I especially want to thank the staff of the electron and light microscopy units, without whom I would have probably infl icted a lot more damage to the equipment and myself.
Also my thanks to Pekka Lappalanen, Erkki Raulo, and Anita Tienhaara of the GSBM, and Eeva Sievi of the VGSB. Their assistance and encouragement over the years have been priceless and our joint expeditions to the outside world will remain unforget-table.
My deepest gratitude also goes to the present and past members of the “yeast group”
Taina, Anna Liisa, Eeva, Ricardo, Ansku, Leena, Hanna, Laura, Anton, Netta, Sergei, Vijay and Mari. In particular I wish to thank both Taina Suntio and Anna Liisa Nyfors for their excellent practical assistance and advice. Without you two, this bird would have never taken off.
And to all my friends and family my absolutely sincere thanks.Your unfl inching support has meant the world to me. Thank you.
Helsinki, 2006
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