Download L04 Proteins

The fluid-mosaic model

Phospholipid bilayer

“Mosaic” of proteins
Proteins

Carry out a cell’s functions:
 Cell division
 Energy generation
 Protein synthesis
 Synthesis of hormones
 Response to hormone signals
 Structure
 Motility
 Recycling of cell materials
 DNA replication
 RNA synthesis
 Transport across membrane
 Transport within cell
 Response to infection
 etc., etc., etc….
“What is the secret of life?” I asked.
“I forget,” said Sandra.
“Protein,” the bartender declared. “They
found out something about protein.“
“Yeah,” said Sandra, “that's it.”
--Kurt Vonnegut in Cat’s Cradle
Proteins

Polymers of amino acids
Amino acids

Side chain gives distinctive chemical properties
Amino acids

Protein = any of 20 amino acids arranged in any order
Protein structure

Amino acids joined by
peptide bonds
Protein structure

Primary (1°) structure = amino-acid sequence
NH2
CH3
+
H3N
CH2
S
O
CH2
C
CH2
OH
H3C
CH2
CH3
CH2 O
H
CH2 O
H
H
O
H
CH2 O
H
CH O
H
CH2 O
C
N
C
N
C
C
N
C
N
C
N
C
C
H
methionine
C
H
aspartate
H
glycine
N-Met-Asp-Gly-Phe-Val-Lys-C
MDGFVK
C
H
phenylalanine
H
valine
C
C
H
lysine
OH
Protein structure

Primary (1°) structure = amino-acid sequence
Lysozyme, 211 amino acids:
MetLeuGlyLysAsnAspProMetCysLeuValLeu
ValLeuLeuGlyLeuThrAlaLeuLeuGlyIleCys
GlnGlyGlyThrGlyCysTyrGlySerValSerArg
IleAspThrThrGlyAlaSerCysArgThrAlaLys
ProGluGlyLeuSerTyrCysGlyValArgAlaSer
ArgThrIleAlaGluArgAspLeuGlySerMetAsn
LysTyrLysValLeuIleLysArgValGlyGluAla
LeuCysIleGluProAlaValIleAlaGlyIleIle
SerArgGluSerHisAlaGlyLysIleLeuLysAsn
GlyTrpGlyAspArgGlyAsnGlyPheGlyLeuMet
GlnValAspLysArgTyrHisLysIleGluGlyThr
TrpAsnGlyGluAlaHisIleArgGlnGlyThrArg
IleLeuIleAspMetValLysLysIleGlnArgLys
PheProArgTrpThrArgAspGlnGlnLeuLysGly
GlyIleSerAlaTyrAsnAlaGlyValGlyAsnVal
ArgSerTyrGluArgMetAspIleGlyThrLeuHis
AspAspTyrSerAsnAspValValAlaArgAlaGln
TyrPheLysGlnHisGlyTyr
Protein structure

Shape is critical to function!
 Enzyme binds substrate
 Antibody binds invading virus
 Transport protein binds specific molecule
HIV Protease
Protein structure

Folding determines 3D shape

Amino-acid sequence determines folding
Lysozyme, 211 amino acids:
MetLeuGlyLysAsnAspProMetCysLeuValLeu
ValLeuLeuGlyLeuThrAlaLeuLeuGlyIleCys
GlnGlyGlyThrGlyCysTyrGlySerValSerArg
IleAspThrThrGlyAlaSerCysArgThrAlaLys
ProGluGlyLeuSerTyrCysGlyValArgAlaSer
ArgThrIleAlaGluArgAspLeuGlySerMetAsn
LysTyrLysValLeuIleLysArgValGlyGluAla
LeuCysIleGluProAlaValIleAlaGlyIleIle
SerArgGluSerHisAlaGlyLysIleLeuLysAsn
GlyTrpGlyAspArgGlyAsnGlyPheGlyLeuMet
GlnValAspLysArgTyrHisLysIleGluGlyThr
TrpAsnGlyGluAlaHisIleArgGlnGlyThrArg
IleLeuIleAspMetValLysLysIleGlnArgLys
PheProArgTrpThrArgAspGlnGlnLeuLysGly
GlyIleSerAlaTyrAsnAlaGlyValGlyAsnVal
ArgSerTyrGluArgMetAspIleGlyThrLeuHis
AspAspTyrSerAsnAspValValAlaArgAlaGln
TyrPheLysGlnHisGlyTyr
Protein structure

Secondary (2°) structure = local folding
a-helix
b-sheet
Protein structure

Held together by non-covalent interactions
Protein structure

Tertiary (3°) structure = overall 3D structure
Protein structure

Tertiary (3°) structure = overall 3D structure
fatty acid
binding protein
myoglobin
CheY
Protein structure

Protein may fold into distinct domains
pyruvate kinase
PEP + ADP →
Pyruvate + ATP
regulatory domain
PEP binding domain
ADP binding domain
Protein structure

Quaternary (4°) structure = intermolecular interaction
Protein structure

Quaternary (4°) structure = intermolecular interaction
Denaturation

Unfolding: disruption of non-covalent interactions
Denaturation

Proteins can be denatured by heating
Denaturation

Proteins have optimum temperature and pH for activity
enzyme from
Listeria bacteria
enzyme from
hot spring bacteria
protein function →
protein function →
enzyme from
human cells
pepsin
yeast
enzyme
37
temperature →
human
hemoglobin
7
pH →
Denaturation

What happens when a protein denatures, or misfolds?
Prions: Pathogens without genes
Normal form of Prion Protein is found in
nerve cells but exact function is unknown.
Abnormal form is folded in “sheets”
rather than helices
Parkinson’s Disease

Loss of dopaminergic neurons of the substantia nigra in the
midbrain.

Loss of motor skills
alpha synuclein
Alpha-Synuclein

Causes Parkinson’s Disease.

Can be passed from cell to cell.
JA Steiner et al. 2011
Fluid-mosaic model

Trans-membrane (integral) proteins

Peripheral membrane proteins
Rhodopsin structure
trans-membrane domain (hydrophobic)
retinal
RPE65 structure