Table Of ContentLaishram Rajendrakumar Singh
Tanveer Ali Dar Editors
Cellular
Osmolytes
From Chaperoning Protein Folding to
Clinical Perspectives
Cellular Osmolytes
Laishram Rajendrakumar Singh
Tanveer Ali Dar
Editors
Cellular Osmolytes
From Chaperoning Protein Folding
to Clinical Perspectives
Editors
Laishram Rajendrakumar Singh Tanveer Ali Dar
University of Delhi Clinical Biochemistry
Dr. B. R. Ambedkar Center for Biomedical University of Kashmir
Research Srinagar
New Delhi Jammu and Kashmir
India India
ISBN 978-981-10-3706-1 ISBN 978-981-10-3707-8 (eBook)
DOI 10.1007/978-981-10-3707-8
Library of Congress Control Number: 2017938881
© Springer Nature Singapore Pte Ltd. 2017
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Contents
1 Osmolyte System and Its Biological Significance . . . . . . . . . . . . . . . . . 1
Pratima Chaudhuri (Chattopadhyay), Naira Rashid,
and Charu Thapliyal
2 Protein-Osmolyte Interactions: Molecular Insights . . . . . . . . . . . . . . 35
Fasil Ali, Usma Manzoor, Mudasser Azam, and Naseem A. Ansari
3 Crosstalk Between Osmolytes and Cellular Chaperones:
Examples in Saccharomyces cerevisiae . . . . . . . . . . . . . . . . . . . . . . . . . 55
Anusha R. Pallapati, Eshita Das, and Ipsita Roy
4 O smolytes Offset the Urea’s Effect on Protein Structure
and Function . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 77
Safikur Rahman, Jihyun Park, and Jihoe Kim
5 O smolytes: Key Players in Regulating Protein Aggregation . . . . . . . 97
Garima Chhabra, Nividh Chandra, and Rajaram Swaminathan
6 Modulation of Protein Aggregation/Fibrillation by Osmolytes . . . . . 121
Mohd Younus Bhat, Laishram Rajendrakumar Singh,
and Tanveer A. Dar
7 Impact of Osmolytes in Conformational Modulation
of Protein and Its Applications in Biotechnology . . . . . . . . . . . . . . . . . 143
Tajalli Ilm Chandel, Mohsin Vahid Khan,
and Rizwan Hasan Khan
8 Clinical Implications of Osmolytes in Various Human Diseases . . . . 161
Sheeza Khan, Tanveer A. Dar,
and Laishram Rajendrakumar Singh
9 Regulation of Cell Volume by Osmolytes . . . . . . . . . . . . . . . . . . . . . . . 195
Yasanandana Supunsiri Wijayasinghe, Arti Tyagi,
and Nitesh Kumar Poddar
10 Bacterial Osmolyte System and Its Physiological Roles . . . . . . . . . . . 229
Iman Dandapath, Megha Chatterjee, Dhoopchhaya Sarkar,
Akanksha Gupta, Gulam Rabbani, and Rinki Minakshi
v
About the Editors
Dr. Laishram R. Singh is an Assistant Professor at the University of Delhi. He
obtained his Master’s degree from Jamia Millia Islamia, New Delhi. After receiving
a doctoral degree in protein biophysics from Jamia Millia Islamia, Dr. Singh contin-
ued his postdoctoral research at Fox Chase Cancer Center, Philadelphia (FCCC).
During his doctoral studies, he was engaged in investigating how small molecule
compounds affect native protein structure, stability, and enzymatic catalysis. At the
FCCC, his main research interest was in understanding the proteostasis and modula-
tors of mutant proteins including mutants of p53, cystathionine beta synthase, and
methyl tetrahydrofolatereductase. Currently, Dr. Singh (at Delhi University) is
investigating how dysregulated proteostasis, which is the common hallmark of
many neurodegenerative and metabolic disorders, could be reversed. A prominent
enzymologist and protein biochemist, Dr. Singh has authored more than 40 publica-
tions in many esteemed journals in the field of proteostatic regulation by small mol-
ecules and various heat shock proteins. He has also contributed chapters to several
books published by Springer, InTech, and Elsevier, etc., and is an active reviewer
and editorial board member of several journals.
Dr. Tanveer A. Dar is a senior Assistant Professor in Clinical Biochemistry at the
University of Kashmir, India. He received his Master’s in Biochemistry from
Hamdard University, New Delhi, India, in 2003 and his PhD in Biosciences from
Jamia Millia Islamia, New Delhi, in 2009. After completing his PhD, he engaged in
a postdoctoral fellowship with Prof. Bruce E. Bowler at the University of Montana,
USA. His main research area is protein structural biology and medicinal plant pro-
teomics. He has published research papers in reputed international journals on pro-
tein folding and its stability in the presence of small molecule solutes. He is a
recipient of Research Fellowships from the CSIR, New Delhi, and the Indian
National Science Academy. Dr. Dar is actively involved in various projects as prin-
cipal investigator and co-investigator with funding from various reputed national
funding agencies, e.g., the Department of Biotechnology and Department of Science
and Technology, Govt. of India, New Delhi. His current research focuses on the
modulation of protein fibrillation/aggregation by chemical chaperones and the char-
acterization of therapeutically important proteins from medicinal plants.
vii
Osmolyte System and Its Biological 1
Significance
Pratima Chaudhuri (Chattopadhyay), Naira Rashid,
and Charu Thapliyal
Contents
1.1 Introduction ....................................................................................................................... 2
1.2 Production, Enhancement and Expression of Osmolytes ............................................... 3
1.2.1 Bacteria and Archaea 6
1.2.2 Yeast 7
1.2.3 Plants 7
1.2.4 Marine Animals 8
1.2.5 Mammals 8
1.3 Mechanism of Interaction of Osmolytes with Proteins ................................................... 11
1.3.1 Role of Naturally Occurring Osmolytes in Destabilizing Proteins 13
1.3.2 Role of Osmolytes in Maintaining Protein Homeostasis 13
1.4 Role of Osmolytes in Protein Aggregation and Amyloidosis ......................................... 14
1.4.1 Mechanism of Aggregation 15
1.4.2 Hypothesis 15
1.5 Role of Osmolytes in Cellular Functions ........................................................................ 18
1.5.1 Role of Osmolytes in Maintenance of Cell Volume 18
1.5.2 Cellular Functions of Osmolytes 19
1.5.3 Protective Effect of Osmolytes on Metabolism 19
1.5.4 Antioxidation 20
1.5.5 Maintenance of Reduction and Oxidation Reactions
and Protection Against Hypoxia 20
1.5.6 Sulfide/Sulfate Detoxification 21
1.5.7 Miscellaneous Roles of Osmolytes in Metabolism 22
1.5.8 Stabilization and Counteraction 22
1.5.9 Anhydrobiosis 23
1.5.10 Freezing 24
1.5.11 High Temperature 24
1.5.12 Hydrostatic Pressure in the Deep Sea 25
1.5.13 The “Yin and Yang” Theory of Cytoprotection 26
P. Chaudhuri (Chattopadhyay) (*) • N. Rashid • C. Thapliyal
Amity Institute of Biotechnology, Molecular Biophysics Laboratory,
Amity University, Sector 125, Noida, Uttar Pradesh 201313, India
e-mail: [email protected]
© Springer Nature Singapore Pte Ltd. 2017 1
L. Rajendrakumar Singh, T.A. Dar (eds.), Cellular Osmolytes,
DOI 10.1007/978-981-10-3707-8_1
2 P. Chaudhuri (Chattopadhyay) et al.
1.6 Role of Osmolytes in Circumventing Stress ..................................................................... 27
1.6.1 Amaranthaceae 28
1.6.2 Plumbaginaceae 28
1.6.3 Plantaginaceae 29
1.6.4 Aizoaceae 29
1.6.5 Poaceae 29
1.6.6 Brassicaceae 29
1.6.7 Other Families 30
1.6.8 Role of Osmolytes in Scavenging Hydroxyl Radicals 30
1.7 Conclusion and Future Directions .................................................................................... 31
References .................................................................................................................................. 31
Abstract
The proper functioning of organisms in stress conditions is an axiological
exercise. Proteins are vulnerable to denaturation and misfolding under hiked
temperatures, increased hydrostatic pressure, the presence of chaotropic agents,
etc. Osmolytes are one of the most important groups of molecules that are
employed by the cell as an adaptation to these harsh conditions. These small
molecules maintain cell volume, osmotic equilibrium, redox states, and energy
quanta of the cell. The current chapter reviews the versatility of the osmolytes in
various metabolic functions and how widely they are distributed across the
different classes of organisms (plants, animals, insects, marine animals, etc.).
This chapter discusses their diversity and the exact mechanism by virtue of
which these osmolytes are able to impart stability to the proteins. It also eluci-
dates on the application of these osmolytes in treatment of various diseases and
as possible drugs from the pharmaceutical point of view.
Keywords
Osmolytes • Diversity • Chaperoneing • Misfolded proteins • Healthcare
1.1 Introduction
The process of protein folding involves attainment of a three-dimensional confor-
mation of protein such that it becomes functional. This three-dimensional structure
is determined by the amino acid sequence. One of the biggest demurring questions
to be investigated is to annotate the mechanism by virtue of which a disorganized
polypeptide chain gets folded to its specific native state. The second half of the
genetic code is yet to be construed. Osmolytes play a significant role in the folding
of proteins in vitro as well as in vivo. Osmolytes bind momentarily to the unstable
conformation of the protein and enable it to fold into the proper three-dimensional
conformations and hence grants stability to the protein structure. Osmolytes not
1 Osmolyte System and Its Biological Significance 3
only help in proper folding of proteins and thereby preventing aggregation and mis-
folding, they also help in protecting the cellular proteins against the stress condi-
tions. The cells come across a number of environmental insults owing to which the
cell tends to lose or accumulate water. Corresponding to the loss or gain of water,
the cell is able to maintain its stability by causing an increase or decrease in the
number of the intracellularly present small osmolytes.
Osmolytes also possess a huge role in prevention of various diseases such as
Huntington’s disease, Alzheimer’s disease, type II diabetes etc. These diseases are
caused due to misfolding of protein or aggregations of proteins. Osmolytes have the
ability to prevent the misfolding of proteins and also inhibit the aggregation of pro-
teins. Hence osmolytes act as vital targets for treatment of the protein misfolding
diseases. The pharmaceutical drug development involving the production of recom-
binant proteins also face challenges due to protein misfolding and aggregation. The
overproduction of recombinant proteins is hampered due to the aggregation and
misfolding of proteins. However, the use of the osmolytes is very fruitful in impart-
ing stability to these recombinant proteins by preventing them from undergoing
misfolding. Hence large-scale hassle-free production of recombinant proteins is
viable by the utilization of osmolytes for this purpose.
Besides, owing to the environmental stresses, the productivity of plants also
depreciates. Various kinds of stresses that cause decrease in the level of water
include extreme temperature, increased concentration of salt in the soil, drought,
etc. On undergoing such harsh environmental abiotic stresses, plants are subjected
to increased production of osmolytes. The increase in production of osmolytes not
only helps in maintaining the cellular hydration of the cell but also helps in main-
taining the metabolic functions of plants which eventually helps in increasing the
productivity of plants.
Osmolytes play an important role in almost all the organisms and help in main-
taining their cellular environment and metabolic functions. They are an essential
class of versatile compounds possessing numerous biological roles which can be
explored for various purposes such as drug development, overproduction of recom-
binant proteins, increasing the productivity of plants, and treating diseases such as
Alzheimer’s disease.
1.2 Production, Enhancement and Expression of Osmolytes
Osmolytes are utilized by diverse organisms to perpetuate their cell volume. They
are small solutes which get accumulated in thermal, pressure, and hydrobiotic
stresses. They are divided into various classes such as sugar alcohols (or polyols),
sugars, amino acids, derivatives of amino acids, methylamines, methylsulfonium
compounds, and urea (Table 1.1). These compounds are usually called as compat-
ible solutes except for urea. The term compatible is used for these compounds
because they do not pronounce any disturbing effect on cell or its biomolecules.
4 P. Chaudhuri (Chattopadhyay) et al.
Table 1.1 Classification of Class of osmolytes Examples
osmolytes into four major
Amino acids Proline
chemical classes
Glycine
Taurine
Lysine
Arginine
Alanine
Ectoine
Methylamines TMAO
Betaine
Sarcosine
Chlorocholine chloride
Choline chloride
Sugars Raffinose
Arabinose
Trehalose
Xylose
Mannose
Galactose
Glucose
Xylose
Polyols Ethylene glycol
Glycerol
Adonitol
Threitol
Arabitol
Sorbitol
Myoinositol
Xylitol
meso-Erythritol
Mannitol
However, there can be certain exceptions to these features. Some of these osmo-
lytes act as antioxidants, thus showing protective role on metabolism, e.g., tau-
rine, hypotaurine, and polyols. Some of them play a role in maintaining redox
balance, e.g., glucose. Osmolytes such as hypotaurine help in detoxifying sulfide
in animals that are present in hydrothermal vents. Some of these compounds are
known to provide stability to macromolecules of cell and work antagonistically
against the perturbants (Yancey 2005) (Fig. 1.1).
