1. “Tracked Step for Step: ATP Splitting in Membrane Protein
Dynamically Measured for the First Time” and “How Cells
Degrade Aberrant Membrane Proteins”
Dariela Cecilia Espinosa Navarro
Medicine Student
School of Health Sciences
University Pontificia Bolivariana
Semester III
2012

2. Medical Utility
The news are displayed in this
Bibliografhy
brochure provide comprehensive Tracked Step for Step: ATP
knowledge and interesting on two Tracked Step for Step: ATP Splitting in Membrane
Splitting in Membrane Protein
processes on the proteins within
Dynamically Measured for the Protein Dynamically
the cell, we can better understand
its mechanisms and how they act First Time. ScienceDaily . July Measured for the First Time
in certain circumstances. 11, 2012 from and How Cells Degrade
http://www.sciencedaily.com/r
eleases/2012/07/1207110741
Aberrant Membrane Proteins
Through these medical 24.htm
breakthroughs achieved to take
How Cells Degrade Aberrant
major steps, the handling of
Membrane Proteins.
Dariela Cecilia Espinosa
proteins and all related elements
allow us to help them to improve ScienceDaily . July 13, Navarro
many diseases. 2012 from Semester III
http://www.sciencedaily.com/r
eleases/2012/07/1207130952
This is important because every 50.htm
day you can manipulate its
operation and prevent risks within MARTINEZ S. LINA MARIA,
Biología molecular. 6 ed.
their respective processes. Having
Medellin; UPB.fac. de Teacher:
awareness of issues as complex
and interesting proteins will allow medicina 2011, p 10-14;42-55. Lina María Martínez
us to approach the world of
science faster and more
effectively.
Julio/2012

3. Introduction
Tracked Step for Step: ATP Splitting in How Cells Degrade Aberrant
Tracked Step for Step: ATP Splitting in Membrane Protein Dynamically Membrane Proteins
Membrane Protein Dynamically Measured for the First Time
Measured for the First Time
July 11, 2012
The researchers observed that the ER rhomboid
In this experiment we can see How a ATP has three phosphate groups. If one protease is increasingly needed during protein
transport protein obtains its driving folding stress. Proteins are produced as long chains
force from the energy storage molecule of these splits off, energy is released. The
transporters are of great medical of amino acids that have to correctly fold into a
ATP, has been tracked dynamically, three-dimensional structure to fulfil their function.
they measured the structural changes significance as they play a central role in Especially when accumulating, misfolded proteins
in the bacterial membrane protein the multi-drug resistance of cancer cells can severely damage cells and are known to cause
MsbA and its interaction partner ATP. impairments such as Alzheimer's and Parkinson's
to chemotherapeutic substances and are
associated with various inherited disease.
By: Prof. Dr. Eckhard Hofmann and According to Dr. Lemberg, these new insights now
Prof. Dr. Klaus Gerwert from the diseases like cystic fibrosis. provide the basis for a molecular understanding of
Biophysics Department report on the The Bochum researchers have now how membrane proteins that make up a large
results in the current issue of the dynamically tracked the ATP splitting, fraction of cellular proteins are extracted from
Journal of Biological Chemistry. called hydrolysis, for the first time in the these membranes for degradation without getting
into each other's way.
fat transporter MsbA from the
How Cells Degrade Aberrant Membrane bacterium Escherichia coli. Using fourier
Proteins transform infrared spectroscopy, they
July 13, 2012 studied the motor domains of MsbA, i.e.
In the second new we can to the part of the protein where the ATP
understand the process of how
damaged proteins are degraded within splitting takes place. Using this method, Student Observation
cells have achieved unexpected researchers can track minute changes in This knowledge is very important because it
insights. Their work focused on the the protein in the range of nanoseconds. allows us to understand how membrane
function of a special protease. This Simultaneously, the method also records proteins make up a large That fraction of
enzyme can hydrolyse peptide bonds in cellular proteins are extracted from These
the plane of cellular membranes, a site changes in the molecules the protein
membranes for Degradation without Into
where such water-requiring reactions interacts with -- in this case ATP. Each Other's getting way. Severely misfolded
commonly do not occur. They could Student Observation
now show that this unusual protease proteins in addition can damage cells and
In this new we can understand how the are Known to cause impairments Such As
recognises and degrades aberrant
proteins directly in the membrane. process is the development of ATP bound Alzheimer's and Parkinson's disease.
to the transport protein, which split off Therefore this study will improve the
By: Researchers from Heidelberg one of three phosphate groups This new is conditions of these diseases and greatly
University's Center for Molecular very important because are associated influences other disease.
Biology (ZMBH) The scientists working with various inherited diseases like cystic
with Dr. Marius Lemberg. fibrosis, which would allow a better study
of this and risk prevention in these cases.

4. Tracked Step for Step: ATP Splitting in How Cells Degrade Aberrant
Membrane Protein Dynamically
Measured for the First Time Membrane Proteins
July 11, 2012 July 13, 2012
In this experiment we can see How a In the second new we can to understand
transport protein obtains its driving force the process of how damaged proteins are
from the energy storage molecule ATP, has degraded within cells have achieved
been tracked dynamically, they measured unexpected insights. Their work focused on
the structural changes in the bacterial the function of a special protease. This
membrane protein MsbA and its enzyme can hydrolyse peptide bonds in the
interaction partner ATP. plane of cellular membranes, a site where
such water-requiring reactions commonly
By: Prof. Dr. Eckhard Hofmann and Prof. do not occur. They could now show that
Dr. Klaus Gerwert from the Biophysics this unusual protease recognises and
Department report on the results in the degrades aberrant proteins directly in the
current issue of the Journal of Biological membrane.
Chemistry.
By: Researchers from Heidelberg
University's Center for Molecular Biology
(ZMBH) The scientists working with Dr.
Marius Lemberg.
INTRODUCTION

5. Tracked Step for Step: ATP Splitting in Membrane
Protein Dynamically Measured for the First Time

6. The Bochum researchers have
now dynamically tracked the ATP
splitting, called hydrolysis, for the
first time in the fat transporter
MsbA from the
bacterium Escherichia coli.
Tracked Step for Step: ATP
Splitting in Membrane Protein
Dynamically Measured for the
First Time

7. ATP splitting: The transport protein
MsbA (grey) splits ATP (coloured),
to generate energy for the transport
process. ATP has three phosphate
groups (orange-red). If one of them
is split off (yellow), energy is
released. The splitting process can
be tracked in the infrared spectrum
(above), in which the various ATP
intermediate products leave
characteristic bands (red: ATP,
yellow: split-off phosphate, white:
protein). (Credit: Falk Syberg
Tracked Step for Step: ATP Splitting in
Membrane Protein Dynamically Measured for
the First Time

8. Phosphate signals reveal what happens during the splitting
 The big challenge presented by the data analysis  the signals in
the measured spectrum to specific molecules or molecular groups.
 Successful  You can see which groups of molecules are
structurally changed and when.
 The biophysicists marked the phosphate groups of the ATP
molecule, so that they left characteristic signals in the spectrum.
Tracked Step for Step: ATP Splitting in
Membrane Protein Dynamically Measured for
the First Time

9.  They tracked  how ATP bound to the
transport protein, how one of its three
phosphate groups split off and was
released into the environment without
first latching back on to the protein.
Tracked Step for Step: ATP Splitting in
Membrane Protein Dynamically Measured for
the First Time

10. In this new we can understand how the
process is the development of ATP bound
to the transport protein, which split off
one of three phosphate groups and
movement of the protein during ATP
hydrolysis and. This new is very important
because are associated with various
inherited diseases like cystic fibrosis,
which would allow a better study of this
and risk prevention in these cases.
STUDENT OBSERVATION

11. How Cells Degrade Aberrant
Membrane Proteins

12.  "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" Dr.
Lemberg.
How Cells Degrade Aberrant
Membrane Proteins

13. How Cells Degrade Aberrant
Membrane Proteins

14. In eukaryotic cells, misfolded
membrane proteins are retained
in the Endoplasmic Reticulum
(ER) as assessed by
immunofluorescence
microscopy. The micrograph
shows a damaged membrane
protein in green and an ER-
resident protein in red leading
to various overlaps in yellow.
•Image: ZMBH
How Cells Degrade Aberrant
Membrane Proteins

15. How Cells Degrade Aberrant
Membrane Proteins

16. This knowledge is very important
because it allows us to understand how
membrane proteins make up a large That
fraction of cellular proteins are extracted
from These membranes for Degradation
without Into Each Other's getting way.
Severely misfolded proteins in addition
can damage cells and are Known to cause
impairments Such As Alzheimer's and
Parkinson's disease. Therefore this study
will improve the conditions of these
diseases and greatly influences our other
disease.
STUDENT OBSERVATION

17.  The news are displayed in this brochure provide
comprehensive knowledge and interesting on two
processes about the proteins within the cell, we can
better understand its mechanisms and how they act in
certain circumstances.
 Through these medical breakthroughs achieved to take
major steps, the handling of proteins and all related
elements allow us to help them to improve many
diseases.
MEDICAL UTILITY

18. This is important because every day you can
manipulate its operation and prevent risks within
their respective processes. Having awareness of
issues as complex and interesting proteins will
allow us to approach the world of science faster
and more effectively.
MEDICAL UTILITY

19.  Tracked Step for Step: ATP Splitting in Membrane
Protein Dynamically Measured for the First Time.
ScienceDaily . July 11, 2012 from
http://www.sciencedaily.com/releases/2012/07/120711074124
 How Cells Degrade Aberrant Membrane Proteins.
ScienceDaily . July 13, 2012 from
http://www.sciencedaily.com/releases/2012/07/120713095250
 MARTINEZ S. LINA MARIA, Biología molecular. 6 ed.
Medellin; UPB.fac. de medicina 2011, p 10-14;42-55.
BIBLIOGRAPHY

20. THANK YOU
Tree of life – Gustav Klimt