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