Vermont Genetics Network Outreach Proteomics Module

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Vermont Genetics Network OutreachProteomics
Module
Proteomics Overview
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What is Proteomics ? or Proteome - ics
? or Protein - omics ?
CREDIT JOE SUTLIFF, Science 291 1221. 2001
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First lets ask, What is Genomics? or
Genome - ics ? or Gene - omics ?
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The Human Genome and the Birth of Genomics
You have likely heard, that not long ago (2001)
the human genome was sequenced. What does this
mean?
Genomics is the study of an organisms
(sometimes a cells or a tissues) DNA
(includes all genes) in its totality.
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OMICS
The term omics is of recent origin but Is now
used by biologists to refer to the study of a
type of molecule or compound in its totality (or
at least on a large scale) Some examples of
omic disciplines are genomics, lipidomics,
metabolomics and proteomics.
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So, now, what is Proteomics? Proteomics is the
study of an organisms (or a cells or a
tissues or an organelles) Proteins in their
totality (or at least on a large scale). So, a
large-scale study of proteins is proteomics.
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What can we learn from seeing things in their
totality that we cant learn from seeing them
individually? What things can we learn from
seeing things individually that we cant see from
seeing them in their totality?
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Technological Advances Help Us See Both the
Forest and the Trees
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Remembering the Central Dogma of biology and
how Inherited information is (most usually)
interpreted by a cell.
DNA
Transcription
( Splicing )
Translation
mRNA
Protein
Smith et al. 2000 Ann. Rev. of Biochem.
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Remembering what a protein is
Protein
Proteins are Polymers of amino acids, whose
unique sequence Gives them unique structures and
thereby unique functions.
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Remembering what an amino acid is
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The Scope of Proteomics
In Humans there are 20,000-25,000 genes (almost
all genes encode proteins). So humans have
20,000-25,000 basic protein types .
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The Scope of Proteomics
However !!! There can be great variability in
proteins due to
? Alternative Splicing
? Post Translational Modifications
? phosphorylation ? methylation ? glycosylation
? ubiquitylation ? acetylation
? Proteolysis
? Polymorphisms (Single Nucleotide Polymorphisms)
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Phosphorylation is a Common Protein
Modification
Humans Devote 653 (roughly 3 of their genes)
to proteins that directly add phosphate
(Kinases) or remove phosphate (Phosphatases).

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The Complexity of Protein Phosphorylation
About 22,000 proteins encoded in the human
genome About 10,000 proteins made in a given
cell type Rough estimates are 1/3 of proteins
are phosphorylated at a given time. If
phosphorylated a protein may average 3
phosphorylation sites There may be then 10,000
Phosphorylation Sites / Cell ! Upper limit for
humans? Estimates are between 66,000 500,000 ?
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Is Protein Modification Important?
ab/ab
ab/ab 2 tyrosine to phenylalanine mutations, or
loss of only 2 hydroxyl groups!
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Is Protein Modification Important?
Red Ys
MSTETELQVAVKTSAKKDSRKKGQDRSEATLIKRFKGEGVRYKAKLIGID
EVSAARGDKLCQDSMMKLKGVVAGARSKGEHKQKIFLTISFGGIKIFDEK
TGALQHHHAVHEISYIAKDITDHRAFGYVCGKEGNHRFVAIKTAQAAEPV
ILDLRDLFQLIYELKQREELEKKAQKDKQCEQAVYQTILEEDVEDPVYQY
IVFEAGHEPIRDPETEENIYQVPTSQKKEGVYDVPKSQPVSAVTQLELFG
DMSTPPDITSPPTPATPGDAFLPSSSQTLPGSADVFGSMSFGTAAVPSGY
VAMGAVLPSFWGQQPLVQQQIAMGAQPPVAQVIPGAQPIAWGQPGLFPAT
QQAWPTVAGQFPPAAFMPTQTVMPLAAAMFQGPLTPLATVPGTNDSARSS
PQSDKPRQKMGKESFKDFQMVQPPPVPSRKPDQPSLTCTSEAFSSYFNKV
GVAQDTDDCDDFDISQLNLTPVTSTTPSTNSPPTPAPRQSSPSKSSASHV
SDPTADDIFEEGFESPSKSEEQEAPDGSQASSTSDPFGEPSGEPSGDNIS
PQDGS
Red Ys
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Examples of Proteomics StudiesWhat Proteins Are
Differentially Produced to Govern Behavior?
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PhosphoproteomicsWhat Proteins are
Phosphorylated Following Various Treatments or In
Different Cell Types or States?
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Identification of Proteins in Embryonic Cerebral
Spinal Fluid What Proteins are in What Tissues?
Zappaterra et al, Journal of Proteome Research,
2007
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Cellular FractionationWhat Proteins are in What
Organelles?
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Proteomic Scientists often seek to understand and
monitor how proteins behave collectively inside a
cellProtein Networks.
Science 3021727 - 1736
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Two Essential Partner Tools in Proteomics