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Phospholipid bilayer “Mosaic” of proteins
The fluid-mosaic model
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….
Proteins
“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
Polymers of amino acids
Proteins
Side chain gives distinctive chemical properties
Amino acids
Protein = any of 20 amino acids arranged in any order
Amino acids
Amino acids joined by peptide bonds
Protein structure
Primary (1°) structure = amino-acid sequenceProtein structure
C CNH3+
CH2
H
N
O
CH2
S
CH3
C C
CH2
H
N
OH
C
O
OH
C C
H
H
N
OH
C C
CH2
H
N
OH
C C
CH
H
N
OH
CH3 CH3
C C
CH2
H
OH
OH
CH2
CH2
CH2
NH2
methionine aspartate glycine phenylalanine valine lysine
N-Met-Asp-Gly-Phe-Val-Lys-C
MDGFVK
Primary (1°) structure = amino-acid sequenceProtein structure
Lysozyme, 211 amino acids:
MetLeuGlyLysAsnAspProMetCysLeuValLeuValLeuLeuGlyLeuThrAlaLeuLeuGlyIleCysGlnGlyGlyThrGlyCysTyrGlySerValSerArgIleAspThrThrGlyAlaSerCysArgThrAlaLysProGluGlyLeuSerTyrCysGlyValArgAlaSerArgThrIleAlaGluArgAspLeuGlySerMetAsnLysTyrLysValLeuIleLysArgValGlyGluAlaLeuCysIleGluProAlaValIleAlaGlyIleIleSerArgGluSerHisAlaGlyLysIleLeuLysAsnGlyTrpGlyAspArgGlyAsnGlyPheGlyLeuMetGlnValAspLysArgTyrHisLysIleGluGlyThrTrpAsnGlyGluAlaHisIleArgGlnGlyThrArgIleLeuIleAspMetValLysLysIleGlnArgLysPheProArgTrpThrArgAspGlnGlnLeuLysGlyGlyIleSerAlaTyrAsnAlaGlyValGlyAsnValArgSerTyrGluArgMetAspIleGlyThrLeuHisAspAspTyrSerAsnAspValValAlaArgAlaGlnTyrPheLysGlnHisGlyTyr
Shape is critical to function! Enzyme binds substrate Antibody binds invading virus Transport protein binds specific molecule
Protein structure
HIV Protease
Folding determines 3D shape Amino-acid sequence determines folding
Protein structure
Lysozyme, 211 amino acids:
MetLeuGlyLysAsnAspProMetCysLeuValLeuValLeuLeuGlyLeuThrAlaLeuLeuGlyIleCysGlnGlyGlyThrGlyCysTyrGlySerValSerArgIleAspThrThrGlyAlaSerCysArgThrAlaLysProGluGlyLeuSerTyrCysGlyValArgAlaSerArgThrIleAlaGluArgAspLeuGlySerMetAsnLysTyrLysValLeuIleLysArgValGlyGluAlaLeuCysIleGluProAlaValIleAlaGlyIleIleSerArgGluSerHisAlaGlyLysIleLeuLysAsnGlyTrpGlyAspArgGlyAsnGlyPheGlyLeuMetGlnValAspLysArgTyrHisLysIleGluGlyThrTrpAsnGlyGluAlaHisIleArgGlnGlyThrArgIleLeuIleAspMetValLysLysIleGlnArgLysPheProArgTrpThrArgAspGlnGlnLeuLysGlyGlyIleSerAlaTyrAsnAlaGlyValGlyAsnValArgSerTyrGluArgMetAspIleGlyThrLeuHisAspAspTyrSerAsnAspValValAlaArgAlaGlnTyrPheLysGlnHisGlyTyr
Secondary (2°) structure = local foldingProtein structure
-helix -sheet
Held together by non-covalent interactionsProtein structure
Tertiary (3°) structure = overall 3D structureProtein structure
Tertiary (3°) structure = overall 3D structureProtein structure
myoglobinfatty acid
binding protein
CheY
Protein may fold into distinct domainsProtein structure
pyruvate kinase
PEP + ADP →Pyruvate + ATP
regulatory domain
PEP binding domain
ADP binding domain
Quaternary (4°) structure = intermolecular interactionProtein structure
Quaternary (4°) structure = intermolecular interactionProtein structure
Unfolding: disruption of non-covalent interactionsDenaturation
Proteins can be denatured by heatingDenaturation
Proteins have optimum temperature and pH for activityDenaturation
temperature →
pro
tein
funct
ion →
pH →pro
tein
funct
ion →
enzyme fromListeria bacteria
enzyme fromhuman cells
enzyme fromhot spring bacteria
pepsin
yeastenzyme human
hemoglobin
737
What happens when a protein denatures, or misfolds?Denaturation
Prions: Pathogens without genesNormal form of Prion Protein is found in nerve cells but exact function is unknown.
Abnormal form is folded in “sheets” rather than helices
Loss of dopaminergic neurons of the substantia nigra in the midbrain.
Loss of motor skills
Parkinson’s Disease
alpha synuclein
Causes Parkinson’s Disease. Can be passed from cell to cell.
Alpha-Synuclein
JA Steiner et al. 2011
Trans-membrane (integral) proteins Peripheral membrane proteins
Fluid-mosaic model
Rhodopsin structure
retinal
trans-membrane domain (hydrophobic)
RPE65 structure