Неструктурированные белки: биофизическая характеристика и биологическая роль (
Конференция по неструктурированным белкам – Intrinsically Unfolded Proteins (IUP) Будапешт, 20–24 мая 2007 г.)
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| Дата: | 2007 |
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| Формат: | Стаття |
| Мова: | Russian |
| Опубліковано: |
Інститут молекулярної біології і генетики НАН України
2007
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| Назва видання: | Біополімери і клітина |
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| Онлайн доступ: | https://nasplib.isofts.kiev.ua/handle/123456789/157533 |
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| Назва журналу: | Digital Library of Periodicals of National Academy of Sciences of Ukraine |
| Цитувати: | Неструктурированные белки: биофизическая характеристика и биологическая роль / Ф.А. Терещенко // Біополімери і клітина. — 2007. — Т. 23, № 3. — С. 260-262. — рос., англ. |
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nasplib_isofts_kiev_ua-123456789-1575332025-02-23T17:11:52Z Неструктурированные белки: биофизическая характеристика и биологическая роль ( Intrinsically Unfolded Proteins: Biophysical characterization and biological significance Неструктуровані білки: біофізична характеристика та біологічна роль Терещенко, Ф.А. Хроніка та інформація Конференция по неструктурированным белкам – Intrinsically Unfolded Proteins (IUP) Будапешт, 20–24 мая 2007 г.) 2007 Article Неструктурированные белки: биофизическая характеристика и биологическая роль / Ф.А. Терещенко // Біополімери і клітина. — 2007. — Т. 23, № 3. — С. 260-262. — рос., англ. 0233-7657 https://nasplib.isofts.kiev.ua/handle/123456789/157533 ru Біополімери і клітина application/pdf application/pdf Інститут молекулярної біології і генетики НАН України |
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Digital Library of Periodicals of National Academy of Sciences of Ukraine |
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DSpace DC |
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Russian |
| topic |
Хроніка та інформація Хроніка та інформація |
| spellingShingle |
Хроніка та інформація Хроніка та інформація Терещенко, Ф.А. Неструктурированные белки: биофизическая характеристика и биологическая роль ( Біополімери і клітина |
| description |
Конференция по неструктурированным белкам – Intrinsically Unfolded Proteins (IUP) Будапешт, 20–24 мая 2007 г.) |
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Article |
| author |
Терещенко, Ф.А. |
| author_facet |
Терещенко, Ф.А. |
| author_sort |
Терещенко, Ф.А. |
| title |
Неструктурированные белки: биофизическая характеристика и биологическая роль ( |
| title_short |
Неструктурированные белки: биофизическая характеристика и биологическая роль ( |
| title_full |
Неструктурированные белки: биофизическая характеристика и биологическая роль ( |
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Неструктурированные белки: биофизическая характеристика и биологическая роль ( |
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Неструктурированные белки: биофизическая характеристика и биологическая роль ( |
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неструктурированные белки: биофизическая характеристика и биологическая роль ( |
| publisher |
Інститут молекулярної біології і генетики НАН України |
| publishDate |
2007 |
| topic_facet |
Хроніка та інформація |
| url |
https://nasplib.isofts.kiev.ua/handle/123456789/157533 |
| citation_txt |
Неструктурированные белки: биофизическая характеристика и биологическая роль / Ф.А. Терещенко // Біополімери і клітина. — 2007. — Т. 23, № 3. — С. 260-262. — рос., англ. |
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Біополімери і клітина |
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Un struc tured Pro teins: bio phys i cal char ac ter iza tion and
bi o log i cal significance
(Con fer ence on In trin si cally Un folded Pro teins (IUP), Bu da pest, May 20-24, 2007)
Un til the re cent time a par a digm that pro teins can
be func tional only af ter fold ing into a de fined
three-di men sional struc ture seemed un dis pu ta ble.
A huge mass of data ques tion ing this dogma has
ap peared dur ing the last ten years. There were dis -
cov ered pro teins that func tion with out as sum ing a
sta bile ter tiary struc ture, and ex ist in so lu tion in a
state tra di tion ally thought as be ing de na tured. It
was Dr. Pe ter Wright (The Scripps Re search In sti -
tute, CA, USA), who boldly stepped for ward in
1999 with the sug ges tion of a pos si bil ity that some
pro teins can nat u rally func tion with out fold ing
into the ter tiary struc ture. It came as a com plete
sur prise that 70% of all eukaryotic pro teins have
un struc tured re gions. As a con se quence of such
ubiq uity of ei ther par tial or com plete lack of struc -
ture, the prob lem of study ing these pro teins, de vel -
op ment of anal y sis meth ods ei ther in vivo, in vi tro
or in silico, no men cla ture is sues, etc. gain sig nif i -
cant im por tance.
IUP – first in ter na tional con fer ence on un struc tured
pro teins – was or ga nized by the lab o ra tory of Dr. Péter
Tompa (In sti tute of Enzymology, Hun gar ian Acad emy
of Sci ences, Bu da pest) with Con fer ence Cen tre of Cen -
tral Eu ro pean Uni ver sity as its venue. The im por tance
of the Con fer ence topic was con firmed by a sheer num -
ber of par tic i pants: 160 vs. 60 ex pected by the or ga niz -
ers.
An open ing talk was given by Dr. Keith Dunker (In -
di ana State Uni ver sity, USA). Com menc ing from the
his tory of the field, he com mu ni cated that the first ideas
and ex per i ments show ing the pos si bil ity of a pro tein
func tion ing with out sta bile de fined ter tiary struc ture
ap peared as early as 1935! A per cent of com pletely or
par tially un struc tured pro teins in eukaryotic proteomes
is high (40 and 70% re spec tively), while prokaryotic
pro teins have more “mod est” unstructuredness. The
main em pha sis of the talk was on the link be tween lack
of struc ture and pro tein func tion (un struc tured pro teins
in ter act with many part ners more of ten which is im por -
tant for sig nal transduction in side a cell); these pro teins
are hubs in interactomes; al ter na tively spliced pro teins
are of ten un struc tured; these pro teins are ex tremely im -
por tant for drug de sign, but are very dif fi cult to deal
with due to in ef fec tive ness of tra di tional dock ing and
ligand li brar ies screen ing soft ware. Prof. Dunker ad -
dressed a ter mi no log i cal is sue as well: he be lieves that a
tra di tional term “in duced fit”, which char ac ter izes ac -
tion mech a nism of un struc tured pro teins, is un ac cept -
able and ad vo cates in stead the term “cou pled bind ing
and fold ing”.
The ses sion of bio phys i cal char ac ter iza tion of in -
trin si cally un struc tured pro teins started with the ple -
nary lec ture of Dr. Pe ter Wright, who em pha sized the
im por tance of NMR as a main bio phys i cal tech nique to
study IUPs, which form a cer tain struc tural con tin uum.
260
ISSN 0233-7657. Biopolymers and cell. 2007. Vol. 23. ISS 3. Translated from Ukrainian.
ã F.A. TERESHCHENKO, 2007
IN FOR MA TION
Dr. Philipp Selenko (Har vard Med i cal School, MA,
USA) dem on strated abil i ties of his unique method of in
vivo NMR for the anal y sis of pro tein dis or der in side a liv -
ing cell. Xenopus oocytes are in oc u lated with la beled pro -
tein and spec tra are re corded. This method con firms ex is -
tence of IUPs in vivo.
Pro fes sor Laurence Barron told about rarely used
method of Raman op ti cal ac tiv ity (ROA), which he ap plies
in his lab at Uni ver sity of Glas gow, UK to the anal y sis of
sec ond ary struc ture con tent and de ter mi na tion of a pro tein
dis or der de gree.
Dr. George Rose (John Hopkins Uni ver sity, MD,
USA) pre sented a time scale and entropic cost of tran si tion
be tween folded and un struc tured state of a pro tein.
Dr. Bojan Žagroviæ (ETH, Zürich, Swit zer land) used
mo lec u lar dy nam ics tech nique for the anal y sis of a
conformational en sem ble as sumed by in trin si cally un -
struc tured pro tein in so lu tion. He uti lized pos si bil i ties of
“Fold ing at home” GRID pro ject to com pute thou sands of
tra jec to ries.
On the ses sion de voted to the link be tween in trin sic
lack of struc ture, pro tein func tion and dis eases Dr. Vladi -
mir Uversky (In di ana State Uni ver sity, IN, USA) lec tured
about im por tance of IUPs for med i cine. Many pro teins
linked to ge netic dis or ders are com pletely or par tially un -
struc tured. Com pletely un struc tured pro tein al -
pha-synuclein, as so ci ated with Par kin son’s dis ease can
serve as a clas si cal ex am ple. Note wor thy, a char ac ter is tic
fea ture of many IUPs is sta bi li za tion of their sec ond ary
struc ture with in crease of tem per a ture or pH!
Dr. Eckhard Mandelkow (Max-Plank-Institut, Ger -
many) de voted his talk to un struc tured pro tein tau, which
causes Alz hei mer dis ease.
Dr. Gary Daughdrill from State Uni ver sity of Idaho,
Mos cow, ID, USA re ported re sults of his study of
conformational en sem bles of p53 transactivation do main
by NMR and mo lec u lar dy nam ics sim u la tion. From the
anal y sis of amino ac ids con tact maps he cal cu lated a set of
most sta tis ti cally prob a ble conformational en sem bles.
A theme of ple nary lection given by Em ily Dim mer
(Wellcome Trust Ge nome Cam pus, UK) was quite dis -
tinct from the oth ers. Pre sent ing the Gene On tol ogy pro -
ject (GO) she spoke about the im por tance for sci en tific
com mu nity to par take, and make an ef fort to the nec es sary
ter mi nol ogy stan dard iza tion (there are about ten dif fer ent
terms solely for the phe nom e non of pro tein struc -
tural dis or der solely).
Dr. Ron ald Wetzel (Uni ver sity of Pitts burgh
School of Med i cine, PA, USA) showed the re sults
of graft ing (he used this very term!) and in ter ac tion
of dis or dered re pet i tive se quences of Hun ting ton
pro tein – a cause of Hun ting ton dis ease.
On the ses sion de voted to bioinformatics char ac -
ter iza tion of dis or der groups of Istvan Si mon (In sti -
tute of Enzymology, Bu da pest), Rob ert Esnouf
(Uni ver sity of Ox ford, UK), Oxana Galtzitskaya
(In sti tute of Pro tein, Pushchino, Rus sia), Szuszanna
Dosztanyi (In sti tute of Enzymology, Bu da pest), Is -
rael Silman (Weizmann In sti tute of Sci ence, Je ru sa -
lem, Is rael), and Monika Fuxreiter (In sti tute of
Enzymology, Bu da pest) pre sented their re sults.
The re search of Da vid Jones (Lon don Uni ver sity
Col lege, Lon don, UK), who is one of the found ers
and ac tive par tic i pants of CASP ex per i ment (Crit i cal
As sess ment of Tech niques for Pro tein Struc ture Pre -
dic tion, by the way, CASP now has a sec tion de -
voted to in trin si cally un struc tured pro teins), is es pe -
cially note wor thy. His pre dic tion method is based on
Dr. Vapnik’s Sup port Vec tor Ma chines (SVM) and
gives sig nif i cant re sults.
Ada Yonath from Weizmann In sti tute of Sci -
ence, Je ru sa lem, Is rael started a ses sion on dis or der
in pro tein-pro tein and pro tein-RNA in ter ac tions by
giv ing a bril liant talk about hy po thet i cal pro tein dis -
or der of ri bo somal pro teins. The au di ence was en -
chanted by a short an i mated film, based on real ex -
per i men tal data and com puter mod el ing, which
dem on strated the mode of work of sev eral ri bo somal
pro teins in the con text of a full ri bo some.
Dr. Péter Tompa showed his re sults sug gest ing
that par tially un struc tured re gions can serve as weak
pro tein deg ra da tion sig nals.
Dr. Gennady Verkhivker (The Uni ver sity of
Kan sas and Uni ver sity of Cal i for nia, San Diego)
an a lyzed strengths and lim i ta tions of com puter
dock ing ap proach to the de sign of lig ands in ter act -
ing with un struc tured pro teins.
In sti tute of Mo lec u lar Bi ol ogy and Ge net ics of
NAS Ukraine (Kyiv) pre sented three post ers by O.
Novosylna et al. The im por tance of in trin sic dis or der
CON FER ENCE ON IN TRIN SI CALLY UN FOLDED PRO TEINS
261
for nor mal and oncogenic isoforms of eEF1A, A.
Kornelyuk et al. Conformational flex i bil ity of un struc -
tured interdomain linker in mam ma lian tyrosyl-tRNA
synthetase stud ied by MD simulatin, and F.
Tereshchenko et al. Dy nam ics of cytokine-like C-ter -
mi nal do main of mam ma lian tyrosyl-tRNA synthetase
at 315K: a tran sient disorer or a mol ten glob ule?. These
works gen er ated a sig nif i cant in ter est.
Talks in couloirs and poster ses sion gave the op por -
tu nity to es tab lish con tacts with many sci en tists work -
ing in this do main of sci ence.
We would like to thank the or ga nizer of the con fer -
ence Dr. Peter Tompa and his group – Denes Kovacs
and Ezster HCzy for a rare in re cent years fault less or -
ga ni za tion of the meet ing.
K&&osz&&on&&om szepen! – Thank you very much!
F.A. Tereshchenko
In sti tute of Mo lec u lar Bi ol ogy and Ge net ics NAS
of Ukraine
TERESHCHENKO F.A.
262
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