A small region in phosducin inhibits G-protein betagamma-subunit
function
K. Bluml, W. Schnepp, S. Schroder, M. Beyermann, M. Macias, H. Oschkinat, and M. Lohse. EMBO J, 16 (16):
4908-15(August 1997)Bluml, K Schnepp, W Schroder, S Beyermann, M Macias, M Oschkinat,
H Lohse, M J Research Support, Non-U.S. Gov't England The EMBO journal
EMBO J. 1997 Aug 15;16(16):4908-15..
Abstract
G-protein betagamma-subunits (G(betagamma)) are active transmembrane
signalling components. Their function recently has been observed
to be regulated by the cytosolic protein phosducin. We show here
that a small fragment (amino acids 215-232) contained in the C-terminus
of phosducin is sufficient for high-affinity interactions with G(betagamma).
Corresponding peptides not only disrupt G(betagamma)-G(alpha) interactions,
as defined by G(betagamma)-stimulated GTPase activity of alpha(o),
but also other G(betagamma)-mediated functions. The NMR structure
of a peptide encompassing this region shows a loop exposing the side
chains of Glu223 and Tyr224, and peptides with a substitution of
either of these amino acids show a complete loss of activity towards
G(o). Mutation of this Tyr224 to Ala in full-length phosducin reduced
the functional activity of phosducin to that of phosducin's isolated
N-terminus, indicating the importance of this residue within the
short, structurally defined C-terminal segment. This small peptide
derived from phosducin, may represent a model of a G(betagamma) inhibitor,
and illustrates the potential of small compounds to affect G(betagamma)
functions.
Bluml, K Schnepp, W Schroder, S Beyermann, M Macias, M Oschkinat,
H Lohse, M J Research Support, Non-U.S. Gov't England The EMBO journal
EMBO J. 1997 Aug 15;16(16):4908-15.
%0 Journal Article
%1 Bluml1997
%A Bluml, K.
%A Schnepp, W.
%A Schroder, S.
%A Beyermann, M.
%A Macias, M.
%A Oschkinat, H.
%A Lohse, M. J.
%D 1997
%J EMBO J
%K & Acid Amino Animals Binding Blotting, Crystallography, Data Eye Fragments/chemistry/metabolism/pharmacology Fusion GTP GTP-Binding Kinases/genetics/metabolism Magnetic Models, Molecular Mutation Peptide Phosphohydrolases/antagonists Phosphoproteins/*chemistry/genetics/metabolism/*pharmacology Protein Proteins/*antagonists Proteins/*chemistry/genetics/metabolism/*pharmacology Proteins/chemistry/metabolism/pharmacology Recombinant Regulators Resonance Secondary Sequence Spectroscopy Structure, Western X-Ray inhibitors/metabolism
%N 16
%P 4908-15
%T A small region in phosducin inhibits G-protein betagamma-subunit
function
%U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9305633
%V 16
%X G-protein betagamma-subunits (G(betagamma)) are active transmembrane
signalling components. Their function recently has been observed
to be regulated by the cytosolic protein phosducin. We show here
that a small fragment (amino acids 215-232) contained in the C-terminus
of phosducin is sufficient for high-affinity interactions with G(betagamma).
Corresponding peptides not only disrupt G(betagamma)-G(alpha) interactions,
as defined by G(betagamma)-stimulated GTPase activity of alpha(o),
but also other G(betagamma)-mediated functions. The NMR structure
of a peptide encompassing this region shows a loop exposing the side
chains of Glu223 and Tyr224, and peptides with a substitution of
either of these amino acids show a complete loss of activity towards
G(o). Mutation of this Tyr224 to Ala in full-length phosducin reduced
the functional activity of phosducin to that of phosducin's isolated
N-terminus, indicating the importance of this residue within the
short, structurally defined C-terminal segment. This small peptide
derived from phosducin, may represent a model of a G(betagamma) inhibitor,
and illustrates the potential of small compounds to affect G(betagamma)
functions.
@article{Bluml1997,
abstract = {G-protein betagamma-subunits (G(betagamma)) are active transmembrane
signalling components. Their function recently has been observed
to be regulated by the cytosolic protein phosducin. We show here
that a small fragment (amino acids 215-232) contained in the C-terminus
of phosducin is sufficient for high-affinity interactions with G(betagamma).
Corresponding peptides not only disrupt G(betagamma)-G(alpha) interactions,
as defined by G(betagamma)-stimulated GTPase activity of alpha(o),
but also other G(betagamma)-mediated functions. The NMR structure
of a peptide encompassing this region shows a loop exposing the side
chains of Glu223 and Tyr224, and peptides with a substitution of
either of these amino acids show a complete loss of activity towards
G(o). Mutation of this Tyr224 to Ala in full-length phosducin reduced
the functional activity of phosducin to that of phosducin's isolated
N-terminus, indicating the importance of this residue within the
short, structurally defined C-terminal segment. This small peptide
derived from phosducin, may represent a model of a G(betagamma) inhibitor,
and illustrates the potential of small compounds to affect G(betagamma)
functions.},
added-at = {2010-12-14T18:12:02.000+0100},
author = {Bluml, K. and Schnepp, W. and Schroder, S. and Beyermann, M. and Macias, M. and Oschkinat, H. and Lohse, M. J.},
biburl = {https://www.bibsonomy.org/bibtex/214f087dd723b56682ef52e04ccbeaaa8/pharmawuerz},
endnotereftype = {Journal Article},
interhash = {37225d6dfbaa779d0cb89ad7cbdf8045},
intrahash = {14f087dd723b56682ef52e04ccbeaaa8},
issn = {0261-4189 (Print) 0261-4189 (Linking)},
journal = {EMBO J},
keywords = {& Acid Amino Animals Binding Blotting, Crystallography, Data Eye Fragments/chemistry/metabolism/pharmacology Fusion GTP GTP-Binding Kinases/genetics/metabolism Magnetic Models, Molecular Mutation Peptide Phosphohydrolases/antagonists Phosphoproteins/*chemistry/genetics/metabolism/*pharmacology Protein Proteins/*antagonists Proteins/*chemistry/genetics/metabolism/*pharmacology Proteins/chemistry/metabolism/pharmacology Recombinant Regulators Resonance Secondary Sequence Spectroscopy Structure, Western X-Ray inhibitors/metabolism},
month = {Aug 15},
note = {Bluml, K Schnepp, W Schroder, S Beyermann, M Macias, M Oschkinat,
H Lohse, M J Research Support, Non-U.S. Gov't England The EMBO journal
EMBO J. 1997 Aug 15;16(16):4908-15.},
number = 16,
pages = {4908-15},
shorttitle = {A small region in phosducin inhibits G-protein betagamma-subunit function},
timestamp = {2010-12-14T18:22:02.000+0100},
title = {A small region in phosducin inhibits G-protein betagamma-subunit
function},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9305633},
volume = 16,
year = 1997
}