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MacromoleculesBIOL222

Ch.3,4,5,and6

Ch.3-Overview:TheMoleculesofLife•  Macromolecules

•  largemoleculescomposedofthousandsofcovalentlyconnectedatoms

•  Builtfromcarbonbackbone

•  AlsocontainlargenumbersofHandO

•  fourclasses:

•  Carbohydrates

•  Lipids

•  Proteins

•  Nucleicacids

MacromoleculesCH3

•  Polymer

•  longmoleculeconsisIngofmanysimilar

subunits

•  Monomers

•  Buildingblocksofpolymers

•  Threeofthefourclassesofmacromoleculesare

polymers:

•  Carbohydrates

•  Proteins

•  Nucleicacids

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•  dehydra>onsynthesis(condensa>on

reac>on)

•  occurswhentwomonomersbond

together

•  throughthecreaIonand

subsequentlossofawater

molecule

•  hydrolysis

•  Processofbreakingpolymers

downtomonomers

•  essenIallythereverseofthe

dehydraIonreacIon

TheSynthesisandBreakdownofPolymersCH3

Short polymer

HO 1 2 3 H HO H

Unlinked monomer

Dehydration removes a water molecule, forming a new bond

HO

H2O

H 1 2 3 4

Longer polymer

(a) Dehydration reaction in the synthesis of a polymer

HO 1 2 3 4 H

H2O Hydrolysis adds a water molecule, breaking a bond

HO H H HO 1 2 3

(b) Hydrolysis of a polymer

TheDiversityofPolymersCH3

2 3 HO H

•  cellsholdhundredsofthousandsof

differentkindsofmacromolecules

•  Humanscanmakeupto

150,000differentproteins

•  Macromoleculardiversity

•  indicaIveofbiological

diversity

•  varietyofpossiblepolymers

virtuallylimitless

•  fromasmallsetofmonomers

CH3

Proteins:Widerangeoffunc>ons

•  Proteins

•  codedinDNA

•  accountformorethan50%ofthedrymassofmostcells

•  ProteinfuncIons

•  structuralsupport

•  storage

•  transport

•  cellularcommunicaIons

•  movement

•  defenseagainstforeignsubstances

CH3

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Polypep>des•  Polypep>des

•  polymersbuiltfromthesamesetof20aminoacids

•  Aminoacidmonomers

•  ProteinconsistsofoneormorepolypepIdes

•  FoldedintofuncIonal3-Dform

CH3

AminoAcidMonomers

•  Aminoacids

•  organicmoleculeswith

carboxylandaminogroups

•  differintheirproperIes

duetodifferingsidechains

•  calledRgroups

Nonpolar

Glycine (Gly or G)

Alanine (Ala or A)

Valine (Val or V)

Leucine (Leu or L)

Isoleucine (Ile or I)

Methionine (Met or M)

Phenylalanine (Phe or F)

Trypotphan (Trp or W)

Proline (Pro or P)

Polar

Serine (Ser or S)

Threonine (Thr or T)

Cysteine (Cys or C)

Tyrosine (Tyr or Y)

Asparagine (Asn or N)

Glutamine (Gln or Q)

Electrically charged

Acidic Basic

Aspartic acid (Asp or D)

Glutamic acid (Glu or E)

Lysine (Lys or K)

Arginine (Arg or R)

Histidine (His or H)

CH3

AminoAcidPolymers

•  pep>debonds

•  CovalentbondbetweenCand

Nlinkingaminoacids

•  PolypepIdes

•  rangeinlengthfromafewto

morethanathousand

monomers

•  Aminoacidsequencedictatestype

ofpolypepIde

•  andulImatelytypeofprotein

Peptide bond

Amino end (N-terminus)

Peptide bond

Side chains

Backbone

Carboxyl end (C-terminus)

(a)

(b)

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ProteinStructureandFunc>on•  funcIonalprotein

•  consistsofone(ormore)polypepIde(s)twisted,folded,andcoiledintoauniqueshape

A ribbon model of lysozyme(a) (b) A space-filling model of lysozyme

GrooveGroove

CH3

•  Sequenceofaminoacids

•  determinesaprotein’sthree-dimensionalstructure

•  Protein’sstructuredeterminesitsfuncIon

•  Fitsubstrateininspecific“lockandkey”fashion

ProteinStructureandFunc>on

Antibody protein Protein from flu virus

CH3

FourLevelsofProteinStructure•  Primarystructure(1°)

•  sequenceofaminoacids

•  Secondarystructure(2°)

•  iniIalfolding

•  alpha(α)helicesorbeta(β)sheetsinthepolypepIdechain

•  TerIarystructure(3°)

•  interacIonsamongsidechains(Rgroups)

•  combinaIonsofα-helicesandβ-sheets

•  Quaternarystructure(4°)

•  proteinconsistsofmul$plepolypepIdechains

CH3

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FourLevelsofProteinStructure•  Primarystructure

•  Sequenceofaminoacids

•  DictatedbysequenceofnucleoIdesinDNA

•  Codon

•  setofthreenucleoIdes

•  codeforaspecificaminoacid

CH3

FourLevelsofProteinStructure

Secondary Structure

β pleated sheet

amino acid subunits

α helix

•  secondarystructure

•  resultfromhydrogenbondsbetweenbackbonesofaminoacids

•  NotRgroups

•  αhelices

•  coiled

•  H-bondbetweeneveryfourthaminoacid

•  αkeraIn-hair

•  βpleatedsheet

•  Accordianfolds

•  AmyloidplaquesofAlzheimers

CH3

•  Ter>arystructure

•  CombinaIonsofhelicesandpleatedsheets

•  determinedbyinteracIonsbetweenRgroups,

ratherthaninteracIonsbetweenbackbone

consItuents

•  covalentbonds

•  hydrogenbonds

•  ionicbonds

•  hydrophobicinterac>ons

•  vanderWaalsinteracIons

•  Strongcovalentbondscalleddisulfidebridges

mayreinforcetheprotein’sstructure

FourLevelsofProteinStructureCH3

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•  Quaternarystructure

•  resultswhentwoormorepolypepIdechainsformonemacromolecule

•  Collagen

•  fibrousproteinconsisIngofthreepolypepIdescoiledlikearope

•  Hemoglobin

•  globularproteinwithfourpolypepIdes:twoalphaandtwobetachains

FourLevelsofProteinStructure

Tertiary Structure Quaternary StructurePolypeptide chain

β Chains

HemeIron

α Chains

CollagenHemoglobin

CH3

Fig.5-21

Primary Structure

Secondary Structure

Tertiary Structure

β pleated sheet

Examples of amino acid subunits

+H3N Amino end

α helix

Quaternary Structure

CH3

WhatDeterminesProteinStructure?

Normal protein Denatured protein

Denaturation

Renaturation

•  InaddiIontoprimarystructure

•  physicalandchemicalcondiIonscanaffectstructure

•  pH

•  saltconcentraIon

•  Temperature

•  otherenvironmentalfactorscancauseaproteintounravel

•  Denatura>on

•  lossofaprotein’snaIvestructure

•  NowbiologicallyinacIve

CH3

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ProteinFoldingintheCell•  Itishardtopredictaprotein’s3Dstructurefromitsprimarystructure

•  Sequencesof1.2millionproteinsknown

•  Only8,5003-Dshapesknown

•  Mostproteinsprobablygothroughseveralstates

•  ontheirwaytoastablestructure

•  Chaperonins

•  proteinmoleculesthatassisttheproperfoldingofotherproteins

Hollow cylinder

Cap

Chaperonin (fully assembled)

Polypeptide

Steps of Chaperonin Action:

An unfolded poly- peptide enters the cylinder from one end.

1

2 3The cap attaches, causing the cylinder to change shape in such a way that it creates a hydrophilic environment for the folding of the polypeptide.

The cap comes off, and the properly folded protein is released.

Correctly folded protein

CH3