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Current
Protein & Peptide Science
ISSN: 1389-2037
Current Protein and Peptide
Science
Volume 9, Number 6, December 2008
Contents
Plasma Gelsolin: Function, Prognostic Value, and Potential
Therapeutic Use
Robert Bucki, Ilya Levental, Alina Kulakowska
and Paul A. Janmey
[Abstract] [Full
text article] [PMID:
19075745 PubMed - indexed for MEDLINE]
Thermal Adaptation of Heat Shock Proteins
A. Muga and F. Moro
[Abstract] [Full
text article]
Advances and Pitfalls in Protein Structure Prediction
D. Cozzetto and A. Tramontano
[Abstract] [Full
text article]
The Hemoglobins of Fishes Living at Polar Latitudes
- Current Knowledge on Structural Adaptations in a Changing
Environment
Cinzia Verde, Alessandro Vergara, Lelio
Mazzarella and Guido di Prisco
[Abstract] [Full
text article]
Flexible Structures and Ligand Interactions of Tandem
Repeats Consisting of Proline, Glycine, Asparagine, Serine,
and/or Threonine Rich Oligopeptides in Proteins
Norio Matsushima, Hitoshi Yoshida, Yasuhiro
Kumaki, Masakatsu Kamiya, Takanori Tanaka, Yoshinobu Izumi
and Robert H. Kretsinger
[Abstract] [Full
text article]
The Retinal cGMP Phosphodiesterase γ-Subunit
— A Chameleon
Lian-Wang Guo and Arnold E. Ruoho
[Abstract] [Full
text article]
Into the Lipid Realm: Stability and Thermodynamics
of Membrane Proteins
Francisco N. Barrera, Luis A. Alcaraz, Estefanía
Hurtado-Gómez and José L. Neira
[Abstract] [Full
text article]
Relaxin and Nitric Oxide Signalling
M.C. Baccari and D. Bani
[Abstract] [Full
text article]
Abstracts
[Back to top]
[Full
text article]
Plasma Gelsolin: Function, Prognostic Value, and Potential
Therapeutic Use
Robert Bucki, Ilya Levental, Alina Kulakowska
and Paul A. Janmey
Gelsolin is a highly conserved, multifunctional actin-binding
protein initially described in the cytosol of macrophages
and subsequently identified in many vertebrate cells. A unique
property of gelsolin is that in addition to its widely recognized
function as a cytoplasmic regulator of actin organization,
the same gene expresses a splice variant coding for a distinct
isoform, plasma gelsolin, which is secreted into extracellular
fluids. The secreted form of gelsolin has been implicated
in a number of processes such as the extracellular actin scavenging
system and the presentation of lysophosphatidic acid and other
inflammatory mediators to their receptors, in addition to
its function as a substrate for extracellular matrix-modulating
enzymes. Consistent with these proposed functions, blood gelsolin
levels decrease markedly in a variety of clinical conditions
such as acute respiratory distress syndrome, sepsis, major
trauma, prolonged hyperoxia, malaria, and liver injury. This
correlation between blood gelsolin levels and critical clinical
conditions suggests the potential utility of gelsolin as a
prognostic marker as well as the possibility for therapeutic
replenishment of gelsolin to alleviate the injurious cascades
in these settings. This review summarizes current data supporting
a role of plasma gelsolin in extracellular fluids and the
potential for its use as a diagnostic marker or therapeutic
treatment in several medical conditions.
[Back to top]
[Full text article]
Thermal Adaptation of Heat Shock Proteins
A. Muga and F. Moro
Heat shock proteins (Hsps) are molecular chaperones that
oppose stress-induced denaturation of other proteins. Hsps
are present in all organisms. Apart from assisting in the
efficient folding of newly synthesized proteins they maintain
pre-existing proteins in a stable conformation, preventing
their aggregation, under stress conditions. The latter role,
essential for thermal adaptation, requires that the chaperone
system change from a folding to a storing function at heat
shock temperatures. The temperature at which this change occurs
depends on the presence of a thermosensor in at least one
of the components of the chaperone systems. In this review,
we focus on the bacterial GroE and DnaK systems, describe
their temperature-sensitive protein components, and the location
of the thermosensor within the structure of these components.
While the thermosensor of the GroE system is located at the
inter-ring interface of GroEL, that of the DnaK system occurs
in its co-chaperone GrpE. Analysis of these examples demonstrates
the amazing mechanistic diversity of thermal stress adaptation
and of functional convergence of structurally unrelated proteins.
[Back to top] [Full
text article]
Advances and Pitfalls in Protein Structure Prediction
D. Cozzetto and A. Tramontano
Three dimensional protein structures are crucial for
understanding biology at both molecular and system level.
Despite the advances in experimental structural biology, the
pace of sequence deposition into databanks considerably exceeds
that of structure determination. Inevitably the functional
annotation of genes and genomes requires the exploitation
of bioinformatics methods for protein sequence comparison
and structure prediction. Hence monitoring objectively the
state of art of the field is of paramount importance, in order
to make best use of computational protein models to address
biological questions. This review describes some relevant
issues in the field of structural bioinformatics, emphasizig
both open basic questions and the progress being continuously
achieved. It is reasonably expected that these bioinformatics
methods will increasingly contribute to the biomedical, pharmaceutical
and biotechnological research.
[Back to top] [Full
text article]
The Hemoglobins of Fishes Living at Polar Latitudes - Current
Knowledge on Structural Adaptations in a Changing Environment
Cinzia Verde, Alessandro Vergara, Lelio
Mazzarella and Guido di Prisco
Fishes thriving in polar habitats offer many opportunities
for comparative approaches to understanding protein adaptations
to temperature. Notothenioidei, the dominant suborder in the
Antarctic Ocean, have evolved reduction of hemoglobin concentration
and multiplicity, perhaps as a consequence of temperature
stability and other environmental parameters. In the icefish
family, the blood pigment is absent. In contrast, similar
to other acanthomorph teleosts, Arctic fish, thriving in a
more complex oceanographic system, have maintained higher
hemoglobin multiplicity and a highly diversified globin system
in response to environmental variability and/or variations
in metabolic demands. This review summarises the current knowledge
on the structure, function and phylogeny of hemoglobins of
fish living in polar habitats. On the basis of crystallographic
analysis, a novel guideline to the interpretation of the Root
effect in terms of a three-state model is suggested, implying
the accessibility of an R/T intermediate quaternary structure,
frequently observed in Antarctic fish hemoglobins. The occurrence
of bis-histidyl and penta-coordinate states in ferric forms
of polar fish hemoglobins suggests additional redox properties.
[Back to top]
[Full text article]
Flexible Structures and Ligand Interactions of Tandem Repeats
Consisting of Proline, Glycine, Asparagine, Serine, and/or
Threonine Rich Oligopeptides in Proteins
Norio Matsushima, Hitoshi Yoshida, Yasuhiro
Kumaki, Masakatsu Kamiya, Takanori Tanaka, Yoshinobu Izumi
and Robert H. Kretsinger
Tandem repeats occur in 14% of all proteins. The repeat
unit lengths range from a single amino acid to more than 100
residues and the repeat number is sometimes over 100. Understanding
the structures, functions, and evolution of these repeats
is a significant goal in both proteomics and genomics. This
review summarizes experimental studies addressing structural
features of tandem repeats of short oligopeptides that are
rich in proline, glycine, asparagine, serine, and/or threonine.
The oligopetides include (PGMG) and (PNN) in biomineralization
protein (PM27), and (NPNA) in Plasmodium falciparum
circumsporozoite protein, (YSPTSPS) in RNA polymerase II,
(PHGGGWGQ) in the prion protein, (YGHGGG(N)) and (YNHGGG(G))
in plant glycine-rich proteins, (PGQGQQ), (PGQGQQGQQ) and
(GYYPTSOQQ) of wheat HMW glutenin, (FGGMGGGKGG) in Aequipecten
abductin. Spectroscopic studies including NMR and CD in-dicate
that these peptides adopt type I and II β-turns,
polyproline II helices, loop conformations, and random coils.
Forma-tion of these structures frequently depends on pH, solvent,
temperature and hydration. The loop conformations are some-times
stabilized by cation-π,
CH-π,
and/or amino-aromatic interactions. These observations indicate
that many tandem repeats are largely flexible. In addition
to generating repeating domains and providing flexible linkers
between domains, the tandem repeats of (PHGGGWGQ), (YGHGGG(N))
and (YNHGGG(G)) and those in titin bind Cu2+ ions; whereas,
tan-dem repeats of (NPNA) and those in elastin bind Ca2+
ions. The interactions of some tandem repeats with various
target proteins probably involve an induced fit. The tandem
repeats in tropoelastin, flagelliform silk, wheat HMW glutenin,
abductin, titin, and human nucleoporin, nup153, are responsible
for elastomeric properties.
[Back to top] [Full
text article]
The Retinal cGMP Phosphodiesterase γ-Subunit—
A Chameleon
Lian-Wang Guo and Arnold E. Ruoho
Intrinsically disordered proteins (IDPs) represent an
emerging class of proteins (or domains) that are characterized
by a lack of ordered secondary and tertiary structure. This
group of proteins has recently attracted tremendous interest
primarily because of a unique feature: they can bind to different
targets due to their structural plasticity, and thus fulfill
di-verse functions. The inhibitory ?-subunit (PDE?) of retinal
PDE6 is an intriguing IDP, of which unique protein properties
are being uncovered. PDE? critically regulates the turn on
as well as the turn off of visual signaling through alternate
interactions with the PDE6 catalytic core, transducin, and
the regulator of G protein signaling RGS9-1. The intrinsic
disor-der of PDE? does not compromise, but rather, optimizes
its functionality. PDE? “curls up” when free in
solution but “stretches out” when binding with
the PDE6 catalytic core. Conformational changes of PDE? also
likely occur in its C-terminal PDE6-binding region upon interacting
with transducin during PDE6 activation. Growing evidence shows
that PDE? is also a player in non-phototransduction pathways,
suggesting additional protein targets. Thus, PDE? is highly
likely to be adaptive in its structure and function, hence
a “chameleon”.
[Back to top]
[Full text article]
Into the Lipid Realm: Stability and Thermodynamics of Membrane
Proteins
Francisco N. Barrera, Luis A. Alcaraz, Estefanía
Hurtado-Gómez and José L. Neira
The first comprehensive studies on the structure and
thermodynamics of membrane proteins have started revealing
the exact architecture of these macromolecules and the physical-chemical
rules behind their structures. In this review, the stabilities
of several families of membrane proteins, obtained by using
spectroscopic, calorimetric and single molecule techniques
are surveyed. The data on the stability of membrane proteins
are compared with those obtained in soluble proteins. The
comparison indicates that although the number of particular
atomic interactions is larger in membrane proteins than in
soluble ones, the overall values are similar. The consensus
is that some intrinsic properties of membrane proteins resemble
those of soluble ones, but there are critical differences
arising form the inter-molecular contacts with the surrounding
membrane. Taken together, all these efforts improve our understanding
of the universal forces governing protein folding, and will
help in the design of membrane proteins in the near future.
[Back to top]
[Full text article]
Relaxin and Nitric Oxide Signalling
M.C. Baccari and D. Bani
The peptide hormone relaxin (RLX) has been shown to exert
a variety of functions in both reproductive and non-reproductive
tissues. The molecular mechanism of RLX on its target cells
appears to involve multiple intracellular signalling systems,
including the nitric oxide (NO) pathway. NO is an ubiquitous
molecule synthesised from L-arginine under the catalytic action
of different nitric oxide synthase (NOS) isoforms and its
altered production has been reported to be involved in several
diseases. RLX has been demonstrated to promote NO biosynthesis
by up-regulating NOS expression; its influence on the different
NOS appears to depend on the cell type studied. In addition
to its physiological roles, RLX has been postulated as a potential
therapeutic agent in several diseases. In particular, based
on its property to promote NO biosynthesis, RLX may be regarded
as a therapeutic tool in diseases characterized pathogenically
by an impaired NO production. The aim of the present mini-review
is to summarize and discuss the pathophysiological actions
of RLX, strictly related to its ability to activate the endogenous
NO pathway in reproductive and non-reproductive target organs.
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