Ph.D. 1989 Max-Planck-Institute for Biochemistry, FRG. Postdoctoral
work at the Max-Planck-Institute for Biophysics, FRG; the Biomedical
Center at the University of Uppsala, Sweden. Group leader in
Structural Biulogy at EMBL 1994-2000. Since 2000 Professor at
BZH, University Heidelberg.
Membrane proteins and protein targeting to membranes
Previous and Current research
We combine X-ray crystallography, spectroscopy and molecular
biology in order to study the mechanism of the proteins of our
A wide range of fundamental biological processes such as energy
and information transport across biological membranes is mediated
by membrane proteins. However, compared to their importance our
knowledge about the three-dimensional structure of these proteins
is very limited. This is mainly due to difficulties in obtaining
well-ordered three-dimensional (3D) crystals from these proteins
and/or problems with the expression. Current projects with membrane
proteins include a number of transport proteins from bacteria
and yeast and G-protein coupled receptors. Our strategies include
the use of monoclonal antibodies for co-crystallization.
Coming from membranes, we got interested in how proteins are
targeted to membranes, and in how they are inserted in or translocated
across membranes. In mammalians targeting of secretory proteins
to the ER membrane is a rather well characterized process. It
involves the signal recognition particle (SRP, a complex of a
7S RNA and six polypeptides ranging from 9 to 72 kDa) and the
SRP receptor. In procaryotes several pathways for protein targeting
exist which meet at the same translocon. In E. coli.,
SRP consists of only one protein (Ffh, p48) and a 4.5 S RNA.
SRP and the SRP receptor are multidomain proteins that contain
a conserved GTP binding domain. We have determined the structures
of several SRP GTPases and we could show that the kinetics of
nucleotide binding are very different from other GTPases. This
implies that the regulation of SRP GTPases is different from
the classical molecular switch model. We have started to assemble
larger complexes of SRP and its receptor form a number of different
sources (including Archaebacteria and the plant chloroplast)
with the aim of structure determination and kinetic characterization.
As far as manpower allows, we are open for collaborations concerning
the structure determin-ation of proteins with interesting mechanisms.
- I. Sinning
- BZH, Im Neuenheimer Feld 328
- D-69120 Heidelberg, Germany
- Fax +49-6221-545586
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Future projects and goals
We continue our efforts with membrane proteins, putting more
emphasis on expression strategies, especially for G-protein coupled
For the SRP project we continue with the structure determination
of other SRP components, especially concentrating on larger complexes
from differenct sources. The aim is to understand how SRP GTPases
regulate the transport of nascent proteins to the membrane and
subsequent translocation or insertion into the membrane.
Interesting projects for predoctoral students:
Structure determination of SRP/SRP receptor complexes and
Structure of the phosphate uptake system in yeast
- Crystal structure of the NG-domain of the signal-recognition
particle receptor FtsY. Montoya, G., Svensson, C., Luirink, J.
& Sinning, I.(1997) Nature 385,365-368.
The signal recognition particle receptor of E. coli (FtsY) has
a nucleotide exchange factor built into the GTPase domsin. Moser,
C., Mol, O., Goody, R.S. & Sinning, I. (1997) PNAS 94, 11339-11344.
Anionic phospholipids are involved in membrane association of
the Signal Recognition Particle receptor FtsY and stimulate its
GTPase activity. de Leeuw, E., te Kaat, K., Moser, C., Menestrina,
G., Demel, R., de Kruijff, B., Luirink, J. & Sinning, I.
(2000) EMBO J. 19, 531-541.
A spectroscopic method for observing the domain movement of the
Rieske iron sulphur protein. Brugna, M., Rodgers, S., Schricker,
A., Montoya, G., Kazmeier, M., Nitschke, W. & Sinning, I.
(2000) PNAS 97, 2069-2074.
The crystal structure of the conserved GTPase of SRP54 from the
archaeon Acidianus ambivalens and its comparison with related
structures suggests a model for the SRP/SR receptor complex.
Montoya, G., te Kaat, K., Moll, R., Schäfer, G. & Sinning,
I. (2000) Structure Fold. Des. 8, 515-525.