of the Max - MDC

Structure of the Group
Group Leader
Dr. rer. nat. Oliver Daumke
Secretariat
Birgit Cloos
Graduate Students
David Schwefel
Song Gao
Technical Assistant
Sabine Werner
Regulation of the tumour suppressor
centaurin-β by liposome binding
GTPase activating proteins (GAP) are off-switches for small
G-proteins, by dramatically stimulating their slow GTP
hydrolysis reaction. In this project, we want to study the
regulation of the centaurin-β family which are GAPs for the
Arf family of small G-proteins. Arfs are implied in various
membrane modulating functions, and the GAP activity of
centaurin-β proteins is greatly stimulated by lipid binding.
We want to obtain structural and mechanistic information
about the GAP activation by lipids and the Arf stimulation by
centaurin-β proteins. Furthermore, centaurin-β proteins
were recently described as tumour suppressors and might be
involved in the regulation of cell motility, and we will use
our structural information to study the cellular function of
these GAPs. The results promise to give new insights in the
function of ArfGAPs during tumour development.
Selected Publications
Daumke, O, Lundmark R, Vallis, Y, Martens, S, Butler, PJ,
McMahon HM. (2007) Architectural and mechanistic insights
into an EHD ATPase involved in membrane remodelling. Nature,
449, 923-927.
Henne, WM, Kent, HM, Ford, MG, Hegde, BG, Daumke, O,
Butler, PJ, Mittal, R, Langen, R, Evans, PR, McMahon, HT.
(2007) Structure and analysis of FCHo2 F-BAR domain: A
dimerizing and membrane recruitment module that effects
membrane curvature. Structure, 15, 839-852.
Kupzig, S, Deaconescu, D, Bouyoucef, D, Walker SA, Liu Q,
Polte, CL, Daumke, O, Ishizaki, T, Lockyer, PJ, Wittinghofer, A,
Cullen PJ. (2006) GAP1 family members constitute bifunctional
RAS and RAP GTPase-activating proteins. J Biol Chem, 281,
9891-9900.
Chakrabarti, PP, Daumke, O, Suveyzdis, Y, Kötting, C,
Gerwert, K, Wittinghofer, A. (2006) Insight into catalysis of a
unique GTPase reaction by a combined biochemical and FTIR
approach. J Mol Biol, 367, 983-985.
a
b
Figure 1a. EHD2 is tubulating
phosphatidyl-serine (PS) liposomes
and oligomerises into ringlike
structures, as analysed by
negative-stain electron microscopy.
Micrographs of PS liposomes
in the absence (top) or presence
(bottom) of EHD2 and
1 mM ATP-γ-S.
c
Figure 1b. Ribbon-type presentation
of the EHD2 dimer. The
structure of EHD2 was determined
by X-ray crystallography. The
two-fold axis is indicted by a
dashed line.
Figure 1c. Top and side view of
the proposed EHD2 oligomer
with the lipid-binding sites of
EHD2 pointing towards the liposome
surface. The EH-domains
are omitted for clarity.
116 Cancer Research