Seminar for PhD students - Max-Planck-Institut für biophysikalische ...

Thomas Güttler
Cellular Logistics
Nuclear transport proceeds through nuclear
pore complexes (NPCs), which are
embedded in the nuclear envelope. Most
nuclear transport pathways are mediated
by importin b-like nuclear transport receptors
that include import mediators
(importins) as well as exportins. CRM1/
Exportin1 is the cell‘s most versatile exportin.
It ferries numerous unrelated cargoes,
which may carry a short leucine-rich
Organizing team: W. Fischle, G. Groenhof, C. Höbartner, S. Jakobs, A. Lange
Cargo recognition by the nuclear export receptor CRM1/Exportin1
Thomas Güttler 1 , Thomas Monecke 2 , Piotr Neumann 2 , Tobias Madl 3,4 , Lorenzo Corsini 3,4 , Achim Dickmanns 2 , Michael Sattler 3,4 , Ralf Ficner 2 , and Dirk Görlich 1
(1) Max-Planck-Institut für biophysikalische Chemie, Abteilung Zelluläre Logistik, Am Fassberg 11, 37077 Göttingen, Germany
(2) Institut für Mikrobiologie und Genetik, Abteilung für Molekulare Strukturbiologie, Georg-August-Universität Göttingen, Justus-von-Liebig-Weg 11, 37077 Göttingen, Germany
(3) Center for Integrated Protein Science Munich, Department Chemie, Technische Universität München, Lichtenbergstrasse 4, 85747 Garching, Germany
(4) Institut für Strukturbiologie, Helmholtz Zentrum München, Ingolstädter Landstrasse 1, 85764 Neuherberg, Germany
nuclear export signal or export signatures
that include folded domains. CRM1
recruits its cargo at high RanGTP levels
in the nucleus, traverses the NPC as ternary
cargo·CRM1·RanGTP complex and
releases its cargo upon GTP hydrolysis in
the cytoplasm. Combining X-ray crystallography
and NMR spectroscopy, we aim to
discover how CRM1 can reconcile specificity
with versatility in cargo recognition
Seite 22
Seminar
Seminar for
for PhD
PhD students
students
7.10.2009
17:00 c.t.
Large seminar room
and how Ran governs cargo loading and
unloading.
The first part of the presentation will focus on
the first crystal structure of a CRM1 export
complex – the snurportin1·CRM1·RanGTP
complex. Snurportin1 is a nuclear import
adapter for cytoplasmically assembled,
m 3G-capped spliceosomal U snRNPs. The
structure shows how CRM1 can specifically
return the cargo-free form of snurportin1
to the cytoplasm. The extensive contact area
includes five hydrophobic residues at
the snurportin1 N-terminus that dock into
a hydrophobic cleft of CRM1, as well
as numerous polar contacts of CRM1 to
m 3G cap-binding domain and C-terminal
residues of snurportin1. The structure suggests
that RanGTP promotes cargo binding
to CRM1 solely through long-range
conformational changes in the exportin.
The second part of the talk will center on
the question as to how CRM1 recognizes
other export cargoes.
References for further reading:
Monecke, T.*, Güttler, T.*, Neumann, P., Dickmanns,
A., Görlich, D., and Ficner, R. (2009)
Crystal structure of the nuclear export receptor
CRM1 in complex with Snurportin1 and
RanGTP. Science 324, 1087-1091.
(*) equal contribution