Fundamental problems of folding. Folding mechanisms of protein molecules

1.

Udmurt State University
Institute of Natural Science
Department of Physiology, Cell biology and Biotechnology
Fundamental problems of
folding.
Folding mechanisms of protein
molecules.
Kunavina Kristina
OAB – 19,03,01-21
Research adviser :
Kozhevnikova Olga Vladimirovna
Foreign language adviser:
Trebuh Olga Sergeevna

2.

In biochemistry and molecular biology, protein folding is the
process of spontaneous folding of a polypeptide chain into a unique
native spatial structure.
Each protein molecule begins to form as a polypeptide translated
from the mRNA sequence in the form of a linear chain of amino
acids. The polypeptide does not have a stable three-dimensional
structure (example on the left side of the image).

3. Chaperones

To ensure folding, a group
of auxiliary proteins called
chaperones is used. They
prevent the interaction of
newly synthesized proteins
with each other, isolate the
hydrophobic portions of
proteins from the
cytoplasm and "remove"
them inside the molecule,
the protein domains are
correctly positioned.

4. Fundamental problems of folding

The problem is that humanity, with all its computing power
and an arsenal of experimental data, still has not learned
how to build models that describe the process of protein
folding and predict the three-dimensional structure of a
protein based on its primary structure (i.e. amino acid
sequence). Thus, there is still no full understanding of this
physical process.

5. What is being done to solve the problem?

There are two groups of structure prediction
methods:
The first includes the so-called modeling methods
“from scratch”
The second group of methods includes
comparative modeling methods.

6. Coagulation mechanisms of protein molecules

Coagulation of the polypeptide
chain into the native
conformation is most successful
under physiological conditions.
The loss of native conformation,
denaturation, occurs at extreme
pH, high temperature or under
the influence of organic solvents,
detergents and other denaturing
substances.

7. Examples

Consider a few examples, globular
proteins built from α-helices, such as
myoglobin, are rare. Usually there are
combinations of folded sheets and spiral
sections, such as, for example, in
flavodoxin, a small flavoprotein, where 5
fan-folded sheets of five parallel strands
form the nucleus of the molecule; 4 αhelical regions surround the core from
the outside. Immunoglobulin is
constructed from several similar domains
(independent, compactly folded
fragments of the polypeptide chain) in
which two antiparallel folded sheets of
three or four strands form a barrelshaped structure.The oligonucleotide
shown in the diagram shows the CH2
domain.

8. Conclusion

The mechanism of protein folding is not fully
understood. The experimental determination of the
three-dimensional structure of a protein is often
very difficult and expensive. However, the amino
acid sequence of a protein is commonly known.
Therefore, scientists are trying to use various
biophysical methods to predict the spatial structure
of a protein from its amino acid sequence.