Download Proteins and Translation

Proteins
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Translation
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Amino acids
Amino acids are the basic structural units of
proteins. All proteins in all organisms are
constructed from 20 primary amino acids.
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Amino acids
The side chains of the amino acids (R) vary in
size, shape, charge, bonding, composition,
and reactivity.
Amino acids are distinguished from one another by their side chains.
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22 proteinogenic amino acids* = 20 primary amino
acids** + pyrrolysine + selenocysteine
*proteinogenic amino acids = amino acids that are found in
proteins and are encoded by a genetic code.
**primary amino acids = found in all proteins in all
organisms
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Zillions of nonproteinogenic amino
acids, e.g., b-naphthylalanine
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There are
20
primary
amino
acids.
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Amino acids
With the exception of glycine (R = H), all amino
acids can form mirror-image enantiomers
around the  carbon: levorotatory (L) and
dextrorotatory (D). In proteins synthesized via
translation of mRNA, only L-amino acids are
used.
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•The smallest amino acid is Gly (molecular weight = 75).
•The largest amino acid is Trp (molecular weight = 204).
•Pro is an an imino acid.
•Three amino acids (Phe, Tyr, Trp) have aromatic side
chains.
•Cys contains a sulfur atom.
•Lys and Arg are positively charged at neutral pH.
•Asp and Glu are negatively charged at neutral pH.
•At pH = 6.0, ~50 percent of His are positively charged;
at pH = 7.0, ~10 percent have a positive charge.
•Gln and Asn are uncharged derivatives of glu and asp,
respectively.
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Venn diagram showing the division of the 20 primary amino acids
into overlapping categories according to size, polarity, charge,
and hydrophobicity. Note that C appears in two distinct places,
as
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reduced cysteine (CH) and as cystine (CS-S).
Proteins: Four levels of structural
organization:
Primary structure
Secondary structure
Tertiary structure
Quaternary structure
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Primary structure = the linear amino acid sequence
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Secondary structure = spatial arrangement of amino-acid
residues that are adjacent in the primary structure
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 helix = A helical structure, whose chain coils
tightly as a right-handed screw with all the side
chains sticking outward in a helical array. The
tight structure of the  helix is stabilized by samestrand hydrogen bonds between -NH groups and
-CO groups spaced at four amino-acid residue
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intervals.
The b-pleated sheet is made of loosely
coiled b strands are stabilized by
hydrogen bonds between -NH and -CO
groups from adjacent strands.
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An antiparallel β sheet. Adjacent β strands run in opposite
directions. Hydrogen bonds between NH and CO groups
connect each amino acid to a single amino acid on an adjacent
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strand, stabilizing the structure.
A parallel β sheet. Adjacent β strands run in the same
direction. Hydrogen bonds connect each amino acid on one
strand with two different amino acids on the adjacent strand.
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Silk fibroin
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Tertiary structure = three-dimensional structure of protein
The tertiary structure is formed by
the folding of secondary structures
by covalent and non-covalent forces,
such as hydrogen bonds,
hydrophobic interactions, salt
bridges between positively and
negatively charged residues, as well
as disulfide bonds between pairs of
cysteines.
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Quaternary structure = spatial arrangement of subunits
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and their contacts.
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Holoproteins & Apoproteins
Holoprotein
Prosthetic group
Apoprotein
Holoprotein
Prosthetic group
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Apohemoglobin = 2 + 2b
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Prosthetic group
Heme
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Hemoglobin = Apohemoglobin + 4Heme
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Christian B. Anfinsen
1916-1995
Sela M, White FH, & Anfinsen CB. 1959. The reductive cleavage
of disulfide bonds and its application to problems of protein
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structure. Biochim. Biophys. Acta. 31:417-426.
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Reducing agents:
Ammonium thioglycolate (alkaline) pH 9.0-10
Glycerylmonothioglycolate (acid) pH 6.5-8.2
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Oxidant
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Intrinsically unstructured proteins,
often referred to as “naturally unfolded
proteins” or “disordered proteins,” are
proteins characterized by a lack of
stable tertiary structure when the
protein exists as an isolated polypeptide
under physiological conditions in vitro.
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Chouard T. 2011. Nature 471:151-153
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Translation
RNA  Protein
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initiation: AUG
mostly
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initiation
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glycylalanine  alanylglycine
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Genetic Codes
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Transcription
Translation
魚  yú  fish
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translation = decoding
Conversion of
information from
one language into
another.
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George Gamow
The Diamond Code (1956)
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translation = decoding
Conversion of information from a language with
a 4-letter alphabet (RNA) into one with a 20-letter
alphabet (protein). What should the conversion
minimal size (codon) be?
1 letter codons  4 possibilities
2 letter codons  16 possibilities
3 letter codons  64 possibilities
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Marshall Nirenberg (right) and Heinrich Matthaei
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Rules of Translation: The “Universal” Genetic Code
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Nonoverlapping Code
AAAAACGAA
lysasnglu
AAAAACGAA
lys lys
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Comaless Code
AAAAACGAA
lys asn glu
AAAAACGAA
lys thr
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Degenerate Code
CTACTCCTG
leu leu leu
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With rare exceptions the genetic code is
Unambiguous Code
CTACTCCTG
leu leu leu
gly tyr ser
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Polysemous = possessing a multiplicity of meaning
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six
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Rules of Translation: The “Universal”
Standard Genetic Code
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The Vertebrate Mitochondrial Genetic Code
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Last Update in NCBI (July 7, 2010):
17 genetic codes
1 standard
8 mitochondrial
16 alternative
5 nuclear
1 both nuclear
& mitochondrial
http://www.ncbi.nlm.nih.gov/Taxonomy/Utils/wprintgc.cgi
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In some organisms, some codons
may never appear in proteincoding genes. These are called
absent codons.
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In some organisms, some codons may not
have appropriate tRNA to pair with. These
codons are called unassigned codons.
Examples:
Codons AGA and AUA are unassigned in
Micrococcus luteus.
Codon CGG is unassigned in Mycoplasma
capricolum.
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Unassigned or Hungry Codons
differ from Stop Codons by not
being recognized by release
factors. Thus, upon
encountering an unassigned
codon, translation stalls, and the
polypeptide remains attached to
the ribosome.
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Flow of information:
transcription
DNA
translation
RNA
Protein
replication
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Flow of information:
DNA
RNA
Protein
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