The researchers were able to crystallize the adenosine A2A receptor protein, a target for caffeine and potentially Parkinson's disease treatments, at the highest resolution ever achieved for a human cell membrane protein. This detailed crystal structure provides insights into how caffeine inhibits the receptor and how water molecules play a role in receptor activation. Additionally, the scientists discovered an enzyme in the cell membrane that recognizes and degrades aberrant membrane proteins, insights that further molecular understanding of protein quality control mechanisms.

1. ANA MILENA SÁNCHEZ HENAO
MEDICINE STUDENT
III SEMESTER
TEACHER:
LINA MARÍA MARTÍNEZ SÁNCHEZ
MOLECULAR BIOLOGY
AUGUST 27

4. The place where the assembly is made
of proteins is the ribosome, which in order to
provide ideal structures and genetically
altered not to remain in perfect condition
and have been properly synthesized
without bad replication of RNAs requiring
programmed control part of the cells to
destroy it if necessary and so prevent a
number of malformations and diseases of
this origin that cause mortality or decreased quality
of life for the population

5. Main receptor
for caffeine in
the human body
Have achieved
the most The protein in This receptor is
detailed crystal question is the also linked to
structure ever Parkinson's
of a target
adenosine A2A disease
protein for receptor
medicines
The class of around
800 proteins to
which the
adenosine A2A
receptor belongs
forms the target for
roughly half of all
medicines

6. To find out whether medicines are
effective, you need to understand how the
receptors in the cell wall work. An
important means of achieving this is to
crystallize the protein, so that it can be
examined with x-rays.
“Since then, a handful of structures of
other receptors have appeared in the
scientific literature, but at such a low
resolution that in some cases it was
even difficult to determine how
medicines bind to such receptors”
“With our new structure, we have
achieved the highest resolution ever
for any protein in the human cell wall”

7. A water channel
in the inactive
receptor
appears to be
disrupted once
it has been
activated. How water
molecules play
a vital role in
activating the
adenosine A2A
receptor
Degree of detail
of the new high-
resolution crystal
structure makes it Hidden site
where a natrium
possible to see ion is
located, away
from the
receptor's drug-
binding cavity.
This gives an insight
into the way natrium
ions affect the
the new high-resolution crystal
working ofpossible to see
structure makes it hormones
and
neurotransmitters in
the body

8. By binding the receptor protein, that is oily and
therefore does not easily crystallize, to another
protein that crystallizes readily, the researchers
were able to produce minuscule crystals of the
fusion product.
Previously, they had used the protein
lysozyme for this process
But this time they used proteins
that crystallize even more easily
and that are a better match for the
receptor
Research indicates that coffee drinkers are
less susceptible to developing Parkinson's
disease. Caffeine has been shown to
inhibit the effect of the receptor, adenosine
A2A, associated with this disorder.

9. I believe the future that this research will therefore have a
clear objective and the results obtained have been very
important and contributors. It seems very interesting , since it
is a breakthrough that supports and strengthens the
scientific studies about the intervention and modification of
proteins that serves as a molecular target for
pharmaceutical treatment of pathologies related, in
addition, these studies can understand the origins of many
diseases and be defined accuracy from molecular biology.

10. Their work focused
on the function of a
special protease
Researchers have
achieved unexpected
insights into the
process of how
damaged proteins
are degraded within
cells.
This enzyme can
this unusual hydrolyze peptide
bonds in the plane
protease of cellular
recognizes and membranes, a site
degrades aberrant where such water-
proteins directly in requiring reactions
the membrane. commonly do not
occur

11. "The existing knowledge about relatives from the
so-called rhomboid protease family did not help
us in our quest for the molecules processed by
the enzyme we discovered," says Dr. Lemberg.
Unlike all rhomboid proteases that had been
studied so far, the new rhomboid localizes to the
Endoplasmic Reticulum (ER), the site in the cell
where new membrane proteins are produced.

12. Alzheimer's
when accumulating, misfolded
proteins can severely damage
cells and are known to cause
impairments such as :
Proteins are produced as long Parkinson's disease
chains of amino acids that
have to correctly fold into a
three-dimensional structure to
fulfill their function
the ER rhomboid protease
The breakthrough came
after the researchers is increasingly needed
observed that : during protein folding
stress

13. "WE NOW HAVE REVEALED THAT THE
ER RHOMBOID PROTEASE CLEAVES
ABERRANT MEMBRANE PROTEINS
WITHIN THEIR MEMBRANE
ANCHOR”, SAYS DR. LEMBERG
The scientists demonstrated that
this protease cooperates directly
with components of the so-called
ER-associated degradation
(ERAD) pathway to dispose of the
faulty protein.

14. These new insights now provide the basis for
a molecular understanding of how
membrane proteins that the make up a large
fraction of cellular proteins are extracted
from these membranes for degradation
without getting into each other’s way

15. Recognize and detect each protein forms a
structure that contributes to better
management of it and thus to better
techniques to modify, create or transform, this
being a good target for treating deadly
diseases

16. Recognize and detect each protein forms a
structure that contributes to better
management of it and thus to better
techniques to modify, create or
transform, this being a good target for
treating deadly diseases may, in this notice
are working with a receiver A2A adenosine
receptor that is a caffeine from the
body, work and handling of the 2A2
receiver released an important preventive
method on Parkinson's disease since it was
discovered that A2A receptor inhibition by
caffeine drinkers in people coffee the risk of
suffering from the disease diminishes what
excellent advances patents on knowledge
and control of diseases that are becoming
increasingly more common in our society.

17. This new is very important because
discovering how to degrade defective
proteins believed to cause metabolic
disorders, cellular and systemic reduces
mortality in human population and the
qualityof life improves and some way to
prolong life

18. Recognize that the accumulation of misfolded proteins can
seriously damage cells causing Alzheimer's and Parkinson
causes the genetic material can be manipulated to reduce
the risk of such diseases or proteins that are targets of
destruction or treatment, which decreases the incidence of
these diseases if detected early.

19. Martinez Sánchez, Lina Maria. “Biología
Molecular” 7ª edition UPB medical faculty
 “Highest Resolution Ever for Human
Protein” .Science daily , July 11 /2012
“How Cells Degrade Aberrant
membrane”. Science daily, July 13 /2012