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““Tracked Step for Step: ATP Splitting in Membrane Protein Tracked Step for Step: ATP Splitting in Membrane Protein Dynamically Measured for the First Time” and “Dynamically Measured for the First Time” and “How Cells How Cells

Degrade Aberrant Membrane Proteins”Degrade Aberrant Membrane Proteins”

Dariela Cecilia Espinosa NavarroMedicine Student

School of Health SciencesUniversity Pontificia Bolivariana

Semester III2012

Tracked Step for Step: ATP Splitting in Membrane Protein Dynamically

Measured for the First Timeand How Cells Degrade

Aberrant Membrane Proteins

Dariela Cecilia Espinosa Navarro

Semester III

Teacher:Lina María Martínez

Julio/2012

Medical Utility

Bibliografhy

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.htm

How Cells Degrade Aberrant Membrane Proteins. ScienceDaily . July 13, 2012 from http://www.sciencedaily.com/releases/2012/07/120713095250.htm

MARTINEZ S. LINA MARIA, Biología molecular. 6 ed. Medellin; UPB.fac. de medicina 2011, p 10-14;42-55.

Bibliografhy




The news are displayed in this brochure provide comprehensive knowledge and interesting on two processes on 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.

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.

How Cells Degrade Aberrant Membrane Proteins

The researchers observed that the ER rhomboid protease is increasingly needed during protein folding stress. Proteins are produced as long chains of amino acids that have to correctly fold into a three-dimensional structure to fulfil their function. Especially when accumulating, misfolded proteins can severely damage cells and are known to cause impairments such as Alzheimer's and Parkinson's disease.According to Dr. Lemberg, these new insights now provide the basis for a molecular understanding of how membrane proteins that make up a large fraction of cellular proteins are extracted from these membranes for degradation without getting into each other's way.

Student ObservationThis knowledge is very important because knowing that misfolded proteins can damage cells and are Severely Known to cause impairments Such As Alzheimer's and Parkinson's disease. This study is a great contribution to modern medicine and the prevention of many other diseases, and interesting management of the proteins that extends the knowledge of these processes and serves to improve the conditions of these diseases.

Introduction


Measured for the First TimeJuly 11, 2012 In this experiment we can see How a

transport protein obtains its driving force from the energy storage molecule ATP, has been tracked dynamically, they measured the structural changes in the bacterial membrane protein MsbA and its interaction partner ATP.

By: Prof. Dr. Eckhard Hofmann and Prof. Dr. Klaus Gerwert from the Biophysics Department report on the results in the current issue of the Journal of Biological Chemistry.


July 13, 2012 In the second new we can to

understand the process of how damaged proteins are degraded within cells have achieved unexpected insights. Their work focused on the function of a special protease. This enzyme can hydrolyse peptide bonds in the plane of cellular membranes, a site where such water-requiring reactions commonly do not occur. They could now show that this unusual protease recognises and degrades aberrant proteins directly in the membrane.

By: Researchers from Heidelberg University's Center for Molecular Biology (ZMBH) The scientists working with Dr. Marius Lemberg.

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

ATP has three phosphate groups. If one of these splits off, energy is released. The transporters are of great medical significance as they play a central role in the multi-drug resistance of cancer cells to chemotherapeutic substances and are associated with various inherited diseases like cystic fibrosis. 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. Using fourier transform infrared spectroscopy, they studied the motor domains of MsbA, i.e. the part of the protein where the ATP splitting takes place. Using this method, researchers can track minute changes in the protein in the range of nanoseconds. Simultaneously, the method also records changes in the molecules the protein interacts with -- in this case ATP.

Student ObservationIn 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 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.

INTRODUCTIONINTRODUCTION


Measured for the First Time


July 11, 2012

In this experiment we can see How a transport protein obtains its driving force from the energy storage molecule ATP, has been tracked dynamically, they measured the structural changes in the bacterial membrane protein MsbA and its interaction partner ATP.

By: Prof. Dr. Eckhard Hofmann and Prof. Dr. Klaus Gerwert from the Biophysics Department report on the results in the current issue of the Journal of Biological Chemistry.

July 13, 2012

In the second new we can to understand the process of how damaged proteins are degraded within cells have achieved unexpected insights. Their work focused on the function of a special protease. This enzyme can hydrolyse peptide bonds in the plane of cellular membranes, a site where such water-requiring reactions commonly do not occur. They could now show that this unusual protease recognises and degrades aberrant proteins directly in the membrane.

By: Researchers from Heidelberg University's Center for Molecular Biology (ZMBH) The scientists working with Dr. Marius Lemberg.

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

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

Tracked Step for Step: ATP Splitting in Tracked Step for Step: ATP Splitting in Membrane Protein Dynamically Measured for Membrane Protein Dynamically Measured for

the First Timethe First Time

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



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.



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.

STUDENT OBSERVATIONSTUDENT OBSERVATION

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

How Cells Degrade Aberrant How Cells Degrade Aberrant Membrane ProteinsMembrane Proteins


"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.


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

STUDENT OBSERVATIONSTUDENT OBSERVATION

This knowledge is very important because knowing that misfolded proteins can damage cells and are Severely Known to cause impairments Such As Alzheimer's and Parkinson's disease. This study is a great contribution to modern medicine and the prevention of many other diseases, and interesting management of the proteins that extends the knowledge of these processes and serves to improve the conditions of these diseases.

MEDICAL UTILITYMEDICAL UTILITY

The news are displayed in this brochure provide The news are displayed in this brochure provide comprehensive knowledge and interesting on two comprehensive knowledge and interesting on two processes about the proteins within the cell, we can processes about the proteins within the cell, we can better understand its mechanisms and how they act in better understand its mechanisms and how they act in certain circumstances. certain circumstances.

Through these medical breakthroughs achieved to take Through these medical breakthroughs achieved to take major steps, the handling of proteins and all related major steps, the handling of proteins and all related elements allow us to help them to improve many elements allow us to help them to improve many diseases. diseases.

MEDICAL UTILITYMEDICAL UTILITY

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

BIBLIOGRAPHYBIBLIOGRAPHY




Tree of life – Gustav KlimtTree of life – Gustav Klimt

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