Prof. Dr. J. Antoinette Killian

 

Location Hugo R. Kruyt building: room W 804
Tel.: +31 30 2533442
Fax: +31 30 2533969
E-mail: j.a.killian@uu.nl
Since 1 May 2002 she is appointed as professor on the chair "Biophysical Chemistry of Membranes" at the Faculty of Chemistry in Utrecht. She participates in the graduate schools IB and Bijvoet.

 
Research

Click here for a short CV
The main research focusses on membrane protein structure. The ultimate aim is to understand and to predict how membrane proteins insert into membranes, which structure they adopt, how they can move, how they interact with other proteins to form oligomeric assemblies, and how this behavior can be influenced by the lipids in the membrane. The strategy to accomplish this is by studying well-defined synthetic model systems of peptides and lipids. These systems mimic biological membranes, but they have the advantage that the properties can be systematically varied and they can be more easily characterized.

The used peptides and proteins vary from designed single a-helices to oligomeric assemblies of synthetic peptides, held together by a scaffold, to intact membrane proteins that spontaneously assemble into stable oligomeric complexes. These peptides or proteins are incorporated into model membranes of lipids with desired properties. The systems are studied either by advanced biophysical techniques, including solid state NMR, fluorescence, calorimetry, circular dichroism and AFM, or by molecular biological approaches.

 

 

Model of a natural oligomeric protein (KcsA) and a single a-helical model peptide (WALP) 

 

Another line of research focusses on amyloid forming proteins, in particular islet amyloid polypeptide (IAPP) involved in type II diabetes. Membranes could play an important role in the lethal action of these proteins, either by catalyzing amyloid formation, and/or by loosing their integrity upon interaction with the proteins and becoming permeable. To gain insight into these possible mechanisms, also here several strategies are used, varying from advanced biophysical techniques and model systems to molecular biological and synthetic approaches.

 

Recent key publications

(For the full list of publications click here)

  1. Holt, A, De Almeida, R.F.M., Nyholm, T.K.M., Loura, L.M.S., Daily, A.E., Staffhorst, R.W.H.M., Rijkers, D.T.S., Koeppe II., R.E., Prieto, M. and Killian, J.A. (2008) Is there a preferential interaction between cholesterol and tryptophan residues in membrane proteins? Biochemistry 47, 2638-2649.
  2. Nyholm TK, Özdirekcan S & Killian JA (2007) How protein transmembrane segments sense the lipid environment. Biochemistry 46, 1457-1465.
  3. Raja, M., Spelbrink, R.E.J., De Kruijff, B. & Killian, J.A. (2007) Phosphatidic acid plays a special role in stabilizing and folding of the tetrameric potassium channel KcsA. FEBS Lett. 581, 5715-5722.
  4. Özdirekcan, S., Etchebest, C., Killian, J.A. and Fuchs, P.F.J. (2007) On the orientation of a designed transmembrane peptide: toward the right tilt angle? J. Am. Chem. Soc. 129, 15174-15181.
  5. Engel MFM, Yigittop H, Elgersma RC, Rijkers DTS, Liskamp RMJ, De Kruijff B, Höppener JWM & Killian JA (2006) Islet amyloid polypeptide inserts into phospholipid monolayers as monomer. J. Mol. Biol. 356, 783-789.
  6. Sparr E, Ash WL, Nazarov PV, Rijkers DTS, Hemminga MA, Tieleman DP & Killian JA (2005) Self-association of transmembrane a-helices in model membranes: Importance of helix orientation and role of hydrophobic mismatch. J. Biol. Chem. 280, 39324-39331.
  7. Özdirekcan S, Rijkers DTS, Liskamp RMJ & Killian JA (2005) Influence of flanking residues on tilt and rotation angles of transmembrane peptides in lipid bilayers. A solid state 2H NMR study. Biochemistry 44, 1004-1012.
  8. Killian JA & Von Heijne G (2000) How proteins adapt to a membrane-water interface. TIBS 25, 429-434.