Übersicht
colloquia - [ 28.06.2005 (11.00) ]
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"Unstructure Determines Function"
Sprecher: Dr. Toby Gibson, Team Leader at European Molecular Biology Laboratory
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In contrast to the physical sciences, there are few binding principles
in biology. The classic dogmas - DNA makes RNA makes protein; One gene
- one enzyme; Structure determines function; – do not operate in sensu
stricto: the latter two are overly restrictive outside the realm of
intermediary metabolism. Enzymes with a single structural domain are a
minority of the proteomes of higher eukaryotes, where a rather fuzzier
dogma is much more typical: one gene > multidomain protein > many
discrete functional segments. Further, with recent estimates that up to
30% of animal proteomes consist of segments of intrinsically
unstructured protein (IUP) that function in a natively unfolded state,
the assertion "Unstructure determines function" cannot be negated in
biochemistry.
There are several varieties of IUP. An increasing number of "induced
fit" modules are being reported by structural biologists: these are
solved in complexes - never, of course, as monomeric structures.
Proteins such as Tau (famous for its role in Alzheimer’s disease) that
lack any native order, point to another role of IUP: as repositories of
probably the most abundant category of protein functional module, the
"linear motifs". These are short peptides that embody autonomous
function independently of tertiary structure. They are used for
regulatory interactions and many are post-translationally modified.
Since linear motifs are statistically insignificant when searching
protein sequences, making them hard to handle, they have been to some
extent ignored by computational biologists. My guesstimate is in the
range 100,000-300,000 instances in the human proteome. The power of
linear motifs in regulatory processes derives from a combination of low
affinity binding interactions, cooperativity, combinatorics and ease of
de novo evolution. I contend that systems biology approaches will not
be widely fruitful until our understanding of the role of linear motifs
in biology has matured.
In my presentation, I will attempt to give a general overview of
multidomain proteins, review the various protein structure classes and
present our tools for protein disorder and linear motifs. I will also
review the currently unsatisfactory state of the teaching material
available in text books for University level teaching. How will the
next generation of researchers be made properly aware of the way that
protein structure is used in cell signaling (and elsewhere too) if they
are not being taught it?
gez. Prof. Dr. Andreas Reuter
http://www.embl-heidelberg.de/~gibson/
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Ort:
Carl-Bosch-Auditorium des Studios der Villa Bosch, 69118 Heidelberg, Schloss-Wolfsbrunnenweg 33 (Eingang Studio - ca. 100 m vom Eingang zur Villa Bosch entfernt, auf der Talseite des Schloss-Wolfsbrunnenweges; Näheres zur Anfahrt siehe unter www.studio.villa-bosch.de.
Parken:
Tiefgarage „Unter der Boschwiese“ (unentgeltlich). Die Einfahrt
befindet sich gegenüber der Abfahrt zur Villa Bosch auf der Bergseite
des Schloss-Wolfsbrunnenweges.
Contact:
Bärbel Mack
EML Research gGmbH
Schloss-Wolfsbrunnenweg 33
69118 Heidelberg
Phone: +49 (0)6221 - 533 - 201
Fax: +49 (0)6221 - 533 - 298
Email: [email protected]
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