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PROTEIN UNFOLDS AND
                                 REFOLDS FOR NEW FUNCTION

                                            AND

                                 BRAIN VARIANTS OF PROTEIN
                              ASSOCIATED WITH HUNTINGTON'S AND
                                 OTHER NEURODEGENERATIVE
                                     DISEASES IDENTIFIED



            By

Maria Alejandra Lugo Posada

      Medical Student

         27/08/12
INTRODUCTION

The gene translation is the step of the information carried by the RNAm to protein; The
last step is traducction embodying the information contained in the DNA, by decoding
order that finally determines the sequence of specific polypeptide chains.
There are some differences between protein synthesis in eukaryotic and prokaryotic
cells: In eukaryotic protein synthesis, it is usually the cytoplasmatic ribosomes that
translate nuclear genes. the ribosomes of eukaryotic cells are larger and contain more
rRNA and protein molecules than those of prokaryotes. in addition, eukaryotes have
more initiation factors and a more complex initiation procedure.
The proteins are active mediators in most cellular processes, carrying out the functions
determined by the information encoded in the DNA.
adequate protein synthesis is of great importance, since large quantities of diseases are
associated with abnormal synthesis these.
Here we will see some news about the proper role of the proteins for their proper
folding, and consequences of polymorphisms.
PROTEIN UNFOLDS AND
                   REFOLDS FOR NEW
                      FUNCTION




So that should work correctly folded proteins in a right way,
and there are certain folds that are more favorable than
others.
In protein folding are two common types: and are the alpha
and beta structure:
•alpha structure in the molecule is coiled in a helix.
•beta structure in the hydrogen bonds are formed between
different parts of the chain more or less parallel to each
other. and going in the same direction and in the opposite
direction.
DNA directed RNA synthesis




RNA directs protein synthesis




      Protein folding




                                  •Catalyze chemical reactions
Protein performs its functions:   •Transmits information between
                                  specific cells
                                  •Participates in the immune
                                  system
                                  •CONTROLS GENE EXPRESSION
Shows that RfaH is even more effective as a
translation factor -- about 100 times more
powerful than it is as a transcription factor.
Because RfaH has more power during translation
because it recruits the ribosome molecule under
circumstances     when      there   isn't   enough
information in the mRNA for the ribosome to do
its protein construction.
Normally the
                       ribosome binds to a
                       specific sequence. If
                             there is no
                       sequence, it doesn't
                       know where to bind.
                        Is believed that the
                       ribosome recognizes
  RfaH can interact
                        RfaH instead of this
 with the ribosome
                       sequence and starts
    once it refolds.
                             translation.
 it can bind to both
the RNA polymerase
and the ribosome at
 the same time and
 link them together
OBSERVATION
An extremely important step in gene translation is the
folding of the protein, since the level agree having
structure and shape as the fold meet or no function, as
is the case RfaH protein that can fulfill two different
functions when folded in two ways different.
we know that proteins are very large and complex
molecules, and each amino acid that composes this at a
specific site, agree to the information of DNA, which
gives the protein necessary for one structure what role
(primary structure, secondary, tertiary and quaternary).
BRAIN VARIANTS OF PROTEIN ASSOCIATED
    WITH HUNTINGTON’S AND OTHER
   NEURODEGENERATIVES DISEASES
             IDENTIFIED

  Was discovered a large new region in
 the genetic code of the protein PGC-
 1alpha. Previously unknown variations
 of the protein, which can be found
 specifically in the brain, are produced
 from this region
.




    A PROMOTER:
    Is a DNA segmente        usually occurring upstream
    from a gene that can ultimately control how that
    gene is expressed as a protein. The transmission of
    genetic    information     from      DNA   to   RNA
    molecules, i.e. transcription, is an important
    intermediate step in this process.
Was demonstrated that these
previously unknown transcripts
 are produced specifically in
 human brain cells and are at
least as common there as the
    reference transcripts.
NEURODEGENERATIVE DISEASES



Are diseases without     Preferred systemic          Are
     evidence of                                                     Prevalence
                        involvement of one       progressive
  exogenous injury                                                 increases with
                          or several neural       character.
(infection, ischemia,                                                   age.
                        systems (substantia
    trauma, etc.).      nigra, hippocampus,
                                 etc)




                                                The cause of neurodegenerative
                                               diseases is often unknown, but is
                                                close relationship with l protein
                                              variation, such as of the PGC-1alpha
                                                             protein.
OBSERVATION

Neurodegenerative diseases such as Huntington's disease, Parkinson's
and Alzheimer's, are diseases affecting much of the population, and are
diseases that have no cure, only methods found that prevented me to
progress so fast, for it is great importance the investigation of causes of
these diseases, in order to guide research in a better way. The discovery
of the variation in the PGC-1alpha protein, provides a way of research.
MEDICAL UTILITY
                  PROTEIN UNFOLDS AND
                REFOLDS FOR NEW FUNCTION


The results about the folding of the

protein have significant implications for

studies of gene expression control and

protein structure.
MEDICAL UTILITY
  PROTEIN UNFOLDS AND
REFOLDS FOR NEW FUNCTION


      In some cases is inefficient translation and in such
      cases proteins are needed to help in this process, as
      is the case Genes that control bacterial virulence are
      famous for being designed in a way that makes their
      translation very inefficient -- hence, they need
      specialized proteins to help their expression
MEDICAL UTILITY
BRAIN VARIANTS OF PROTEIN ASSOCIATED WITH HUNTINGTON’S AND
       OTHER NEURODEGENERATIVES DISEASES IDENTIFIED


    The protein PGC-1 alpha is a protein with many essential functions in our
    body, but is also associated with diseases neurodegenerative wherefore it
    is of great clinical importance because in a way that guides the study for
    the cure of these diseases.
MEDICAL UTILITY
BRAIN VARIANTS OF PROTEIN ASSOCIATED WITH HUNTINGTON’S AND
      OTHER NEURODEGENERATIVES DISEASES IDENTIFIED


     The promoter is a control element, which is recognized
     by the RNA polymerase to begin transcription, and found
     a new promoter that is active in the nervous system, and
     which interferes with transcription to the gene coding for
     protein PGC-1 alpha, so we see that in this study of
     neurodegenerative diseases is also of great importance
     to study the promoters.
REFERENCES
•   Voet, D. fundamentos de bioquimica.2° Edición. Editorial panamericana.
    Argentina.2007. 161 p.

•   CLARK, D. Molecular Biology. Editoriar Elsevier. California. 2005. Pag 281

•   TEIJN, J, M; GUERRIDO,A; BLANCO; D. Fundamentos de bioquímica metabólica.
    2° Edición. Editorial Tebar.Madrid.2006 .Pag 321

•   MARTINEZ SÁNCHEZ, Lina María. Biología molecular. 7°. ed. Medellín: UPB. Fac.
    de Medicina, 2012. 106 p.

•   BLAZQUEZ, E. Fundamentos moleculares de la medicina 1. Editorial real academia
    nacional de medicina. 161 p.
PROTEIN UNFOLDS AND REFOLDS FOR NEW FUNCTION and BRAIN VARIANTS OF PROTEIN ASSOCIATED WITH HUNTINGTON'S AND OTHER NEURODEGENERATIVE DISEASES IDENTIFIED

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PROTEIN UNFOLDS AND REFOLDS FOR NEW FUNCTION and BRAIN VARIANTS OF PROTEIN ASSOCIATED WITH HUNTINGTON'S AND OTHER NEURODEGENERATIVE DISEASES IDENTIFIED

  • 1. PROTEIN UNFOLDS AND REFOLDS FOR NEW FUNCTION AND BRAIN VARIANTS OF PROTEIN ASSOCIATED WITH HUNTINGTON'S AND OTHER NEURODEGENERATIVE DISEASES IDENTIFIED By Maria Alejandra Lugo Posada Medical Student 27/08/12
  • 2.
  • 3.
  • 4. INTRODUCTION The gene translation is the step of the information carried by the RNAm to protein; The last step is traducction embodying the information contained in the DNA, by decoding order that finally determines the sequence of specific polypeptide chains. There are some differences between protein synthesis in eukaryotic and prokaryotic cells: In eukaryotic protein synthesis, it is usually the cytoplasmatic ribosomes that translate nuclear genes. the ribosomes of eukaryotic cells are larger and contain more rRNA and protein molecules than those of prokaryotes. in addition, eukaryotes have more initiation factors and a more complex initiation procedure. The proteins are active mediators in most cellular processes, carrying out the functions determined by the information encoded in the DNA. adequate protein synthesis is of great importance, since large quantities of diseases are associated with abnormal synthesis these. Here we will see some news about the proper role of the proteins for their proper folding, and consequences of polymorphisms.
  • 5. PROTEIN UNFOLDS AND REFOLDS FOR NEW FUNCTION So that should work correctly folded proteins in a right way, and there are certain folds that are more favorable than others. In protein folding are two common types: and are the alpha and beta structure: •alpha structure in the molecule is coiled in a helix. •beta structure in the hydrogen bonds are formed between different parts of the chain more or less parallel to each other. and going in the same direction and in the opposite direction.
  • 6. DNA directed RNA synthesis RNA directs protein synthesis Protein folding •Catalyze chemical reactions Protein performs its functions: •Transmits information between specific cells •Participates in the immune system •CONTROLS GENE EXPRESSION
  • 7. Shows that RfaH is even more effective as a translation factor -- about 100 times more powerful than it is as a transcription factor. Because RfaH has more power during translation because it recruits the ribosome molecule under circumstances when there isn't enough information in the mRNA for the ribosome to do its protein construction.
  • 8. Normally the ribosome binds to a specific sequence. If there is no sequence, it doesn't know where to bind. Is believed that the ribosome recognizes RfaH can interact RfaH instead of this with the ribosome sequence and starts once it refolds. translation. it can bind to both the RNA polymerase and the ribosome at the same time and link them together
  • 9. OBSERVATION An extremely important step in gene translation is the folding of the protein, since the level agree having structure and shape as the fold meet or no function, as is the case RfaH protein that can fulfill two different functions when folded in two ways different. we know that proteins are very large and complex molecules, and each amino acid that composes this at a specific site, agree to the information of DNA, which gives the protein necessary for one structure what role (primary structure, secondary, tertiary and quaternary).
  • 10. BRAIN VARIANTS OF PROTEIN ASSOCIATED WITH HUNTINGTON’S AND OTHER NEURODEGENERATIVES DISEASES IDENTIFIED Was discovered a large new region in the genetic code of the protein PGC- 1alpha. Previously unknown variations of the protein, which can be found specifically in the brain, are produced from this region
  • 11. . A PROMOTER: Is a DNA segmente usually occurring upstream from a gene that can ultimately control how that gene is expressed as a protein. The transmission of genetic information from DNA to RNA molecules, i.e. transcription, is an important intermediate step in this process.
  • 12. Was demonstrated that these previously unknown transcripts are produced specifically in human brain cells and are at least as common there as the reference transcripts.
  • 13. NEURODEGENERATIVE DISEASES Are diseases without Preferred systemic Are evidence of Prevalence involvement of one progressive exogenous injury increases with or several neural character. (infection, ischemia, age. systems (substantia trauma, etc.). nigra, hippocampus, etc) The cause of neurodegenerative diseases is often unknown, but is close relationship with l protein variation, such as of the PGC-1alpha protein.
  • 14. OBSERVATION Neurodegenerative diseases such as Huntington's disease, Parkinson's and Alzheimer's, are diseases affecting much of the population, and are diseases that have no cure, only methods found that prevented me to progress so fast, for it is great importance the investigation of causes of these diseases, in order to guide research in a better way. The discovery of the variation in the PGC-1alpha protein, provides a way of research.
  • 15. MEDICAL UTILITY PROTEIN UNFOLDS AND REFOLDS FOR NEW FUNCTION The results about the folding of the protein have significant implications for studies of gene expression control and protein structure.
  • 16. MEDICAL UTILITY PROTEIN UNFOLDS AND REFOLDS FOR NEW FUNCTION In some cases is inefficient translation and in such cases proteins are needed to help in this process, as is the case Genes that control bacterial virulence are famous for being designed in a way that makes their translation very inefficient -- hence, they need specialized proteins to help their expression
  • 17. MEDICAL UTILITY BRAIN VARIANTS OF PROTEIN ASSOCIATED WITH HUNTINGTON’S AND OTHER NEURODEGENERATIVES DISEASES IDENTIFIED The protein PGC-1 alpha is a protein with many essential functions in our body, but is also associated with diseases neurodegenerative wherefore it is of great clinical importance because in a way that guides the study for the cure of these diseases.
  • 18. MEDICAL UTILITY BRAIN VARIANTS OF PROTEIN ASSOCIATED WITH HUNTINGTON’S AND OTHER NEURODEGENERATIVES DISEASES IDENTIFIED The promoter is a control element, which is recognized by the RNA polymerase to begin transcription, and found a new promoter that is active in the nervous system, and which interferes with transcription to the gene coding for protein PGC-1 alpha, so we see that in this study of neurodegenerative diseases is also of great importance to study the promoters.
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