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- Year1(Salmon)
NaturalSciences
Biological
Molecules- Proteins
A m i n oa c i d sa r et h e m o n o m e r so f a l l p r o t e i n sA. l l a m i n oa c i dm o l e c u l ecso n t a i na t o m so f c a r b o n ,
hydrogenand oxygentogetherwith nitrogen.Somealsocontainsulphur.Aminoacidscondense
togetherto form longchainsknownas polypeptides.
A proteinmoleculeconsistsof one or morethan
o n e p o l y p e p t i dceh a i n .
Proteinsarethereforea groupof organiccompoundswhosemolecules
consistof carbon,hydrogen,
oxygen,nitrogenand sometimessulphuratoms.Theyare condensation
polymersof aminoacids.
E a c ha m i n oa c i dc o n t a i n a
s c a r b o x y l g r o uapn da n a m i n og r o u p T
. h ep a r to f t h e m o l e c u l e
w h i c hi s
differentin everyaminoacidis knownasthe R-group.The R-groupcanvaryenormously.SomeRgroupsare polar,someare non-polar,somecontaincarboxylgroupsand somecontainhydroxylgroups.
A few, suchas cysteine,
containsulphur.
Humanscan producesomeaminoacidsin the bodyby conversion
from others.However,somemust be
eatenas part of our diet.Theseare calledessentialaminoacids.
'

Behaviourof amino acidsin water

Whenan aminoaciddissolves
in water,the carboxylgroupdissociates,
freeinga hydrogenion,so
becomingnegatively
charged.Meanwhilethe aminogroupacquiresa hydrogenion and becomes
positively
charged.Thereforethe ion formedhasboth a negativeand a positivechargeand is calleda
zwitterion.
Theabilityto take up hydrogenionsfrom a solutionenablesthe aminoacidsto take up hydrogenions
readilyfrom an acidsolution,so makingthe solutionlessacid.Aminoacidsreleasehydrogenionsreadily
i n a l k a l i n ce o n d i t i o n ss,o m a k i n gt h e s o l u t i o nl e s sa l k a l i n eF. o rt h i sr e a s o nt,h e a m i n oa c i dc a na c ta s a
pH buffer.A pH bufferis a substance
whichcan resista changein the acidityor alkalinityof its
surroundings.
Condensation
of amino acids
Two aminoacidscondensetogether,to form a dipeptide.The bondwhichis formed,linkingthe amino
acids,is calleda peptidebond.
Furthercondensation
reactionsbetweenaminoacidsleadto the formationof longchainscalled
polypeptides.
Aminoacidsmay condensein anyorderand form chainsof any length.All polypeptide
chainsformedwill havesimilar'backbones'
containingpeptidebonds.Everypolypeptidehasan 'amino
'carboxyl
end' with an aminogroupand a
end' with a carboxylgrouppresent.Howeverthe orderof Rgroupsalongdifferentchainsvaries.

Therearetwentydifferentaminoacidsavailable
and polypeptide
chainsmay be formedwith any
numberand any differentorderof arninoacids.Thereforeit is possibleto form an infinitenumberof
with d ifferentproperties.
d ifferent polypeptides
Theorderof R-groups
alongthe polypeptide
dependsuponthe sequenceof aminoacidsforming
monomersin the chain.Everydifferentpolypeptideis formedfrom a differentsequenceof aminoacids.
whichdeterminesthe shapeand the propertiesof the polypeptide.
It is thisorderof R-groups
Levelsof protein structure
Primarystructureof proteins
within a proteinmolecule.Only
Thisrefersto the exactsequenceof aminoacidsin the polypeptide(s)
peptidebondsare involvedin formingthis sequence.
Secondarystructureof proteins
Hvdroaenbonds
Partsof the backboneof everypolypeptidecarrysmallpositiveor negativecharges.
form betweenthesecharges.
Thesecondary
structurerefersto the shapein all polypeptides,
the sameshapecan be takenup by
(or part of them).Thereforethe shapeis not specificto particularpolypeptides.
differentpolypeptides
T h es h a p ei s r e g u l aar n d i s r e p e a t e da l o n gt h e c h a i n .
Thetwo mostcommontypesof secondary
structureare the alpha-helix
and the beta-pleated
sheet.
ln the alpha-helix,
the hydrogenbondsare formedbetweenthe COof one aminoacidwith the NH of an
p
l
a
c e sf u r t h e ra l o n gt h e c h a i nT
a m i n oa c i df o u r
. h i st w i s t st h e c h a i ni n t oa s p i r a (l h e l i c a fl )o r m w h e r et h e
'twists'areheldin placeby
the hydrogenbonds.Justa smallportionof a shortchainmay take up this
or longchainsmay becometwistedinto an alpha-helix
configuration
alongthe whole length.Keratin,
t h e i n s o l u b l pe r o t e i no f h a i r ,n a i l sa n df e a t h e r sh, a sm o l e c u l ews h i c ha r e l a r g e l yi n t h i ss h a p e .
In the beta-pleated
sheet,adjacentportionsof differentpolypeptide
chains,if formed in opposite
directions
to eachother (anti-parallel),
may form a beta-pleated
sheet.Hydrogenbondsform between
the -CO groupsof one chainand the -NH groupsof neighbouring
chains.Thisgivesa stronger,but less
elasticstructurethan the alpha-helix.
An exampleof a proteinwith a structurelargelybaseduponthe
beta-pleated
sheetis the proteinwhichmakesup silk(fibrion).

The tertiary structureof proteins

Thisrefersto the shapetakenup by the polypeptide
chain(s)of someproteinsas a resultof various
bondsbetweenpartsof the R-groupsof the chains.As everydifferentpolypeptidehasa differentorder

of R-groups,
the bondsform in differentplacesin everydifferentpolypeptide,
leadingto different
shapes.
Therearethreetypesof bond which may be formedbetweenR-groups,
and theseare mainly
polypeptide
for foldinga
responsible
into its tertiarystructure.Theyare the hydrogenbond,the ionic
b o n d ,a n dt h e d i s u l p h i dbeo n d .
fhe hvdroaenbond is very commonbut is the weakestof the three bonds.lt is formedwhen the
H atomsof the -OH or -NH of one R-groupattractthe electronegative
electropositive
O of a COgroupin
a n o t h e rR g r o u p .
lonicbondsform betweenaminoand carboxylpartspresenton someR-groups.
Theseare strongerthan
hydrogen
b o n d sb u t i n w a t e rt h e ya r e m u c hw e a k e rt h a nt h e d i s u l p h i dbeo n d .
Thedisulphidebond is a covalentbondwhichis formedbetweenthe R-groups
of aminoacidssuchas
-SH
groups.Thisis the strongestbondof the three.
cysteinewhichhave
Theshapewhichthe chaintakesup is alsoaffectedby the presence
R-groups
whichtend
of hydrophobic
to take up a positionawayfrom water protectedby other partsof the molecule.Hvdrophobic
. interoctionsoccurbetweensuchgroups.
A l l o f t h e s eb o n d sa n d i n t e r a c t i o nt se n dt o c a u s et h e p r o t e i nt o f o l d i n t o a n i r r e g u l a rc,o m p a c tg, l o b u l a r
s h a p ew i t h h y d r o p h i l ipca r t so n t h e o u t s i d ei n a n a q u e o u se n v i r o n m e nO
t . n em o l e c u l em a y b e c o m e
'shell'of
water moleculesand becomeseparated
surroundedby a
from others.Suchproteinsare saidto
'colloidal'
be solubleforminga
solution.Theyare referredto asglobularproteins.An exampleof a
globularproteinis insulin.Partsof a polypeptide
whichfold in this way,may alreadybe in the form of an
alpha-helix
or beta-pleated
sheet.
Thetertiarystructureof everydifferentpolypeptide
is different.The shapeis saidto be specific.The
f u n c t i o no f t h e p r o t e i nd e p e n d su p o nt h i ss h a p e .
Not allproteinsfold into a tertiarystructure,especially
if they havevery longpolypeptidechainsrichin
h y d r o p h o b iacm i n oa c i d sP
. r o t e i n s u c ha s k e r a t i nc, o l l a g e a
n n df i b r o i na r e i n s o l u b l ae n dt h e m o l e c u l e s
are unfoldedand havea non-specific
fibrousstructure.Theyare referredto asfibrousproteins.

Quaternarystructureof proteins
Someproteinsare madeof more than one polypeptide
chain.Thesechainsinteractwith eachother.The
quaternarystructurerefersto this structurein whichmorethan two or more polypeptidechainsare
interacting.
Thisstructureis stabilizedby the bondsand interactions
whichstabilizethe tertiary
structure.E.g.Haemoglobin

Conjugated proteins
proteinshavemoleculesin whichpolypeptide
Conjugated
chain(s)are linkedto a non-proteinpartof
the molecule.
The non-proteinpart is calledthe prostheticgroup.
An exampleof a conjugatedproteinis
h a e m o g l o b iT
nh
. i sm o l e c u l ec o n t a i n fso u r p o l y p e p t i dceh a i n sa n df o u r h a e mg r o u p s .
The 'stability'of proteins
A moleculeis regardedas chemically
stableif it doesnot reactwith other chemicals
readily,and is not
changee
d a s i l yb y c h a n g i n cgo n d i t i o n ss,u c ha st e m p e r a t u r e .
Thetertiaryshapeof globularproteinsand,therefore,theirvital propertiesare easilyaltered.Theshape
is dependentuponweak hydrogenand ionicbonds.A risein temperaturecausesthe molecules
to
vibratemore.Thisdisruptsthe hydrogenbondsand,asthey break,the shapeof the moleculealters.
The hydrogenbondsand ionicbondsare alsoaffectedby a changein pH of the solutionbecausethe
changesin concentration
of the positively
chargedhydrogenionsaffectthe forcesof attractionholding
p
r
o
t
e
i
n
the
m o l e c u l ei n s h a p e .
g l o b u l apr r o t e i n si n s o l u t i o na r e u n s t a b l e
a st h e i rs h a p ei s e a s i l yc h a n g e dl .f t h i sh a p p e n st ,h e y
, So,
cannotcarryout their functionsand they are saidto be denatured.Thisis very significant
if the globular
proteinsare enzymes.
The insoluble
fibrousproteinsare muchmore stable.
Collagen
Collagen
is an importantfibrousprotein.lt is a majorcomponentof the connective
tissuesof the bodies
of manyanimals.Connective
tissueshold othertissuestogetherand are found,for examplein tendons,
bloodvesselwallsand fibresholdingteeth in gums.Collagen
is alsoimportantin bonewhereit binds
inorganic
crystalstogether,preventingthe bonesfrom beingbrittleand easilybroken.
Thecollagenmoleculeis very stableand extremelystrong.Eachmoleculeconsistsof three polypeptide
chainswoundroundeachotherto form a triplehelix(likethe strandsof a ropetwinedaroundeach
other).Theaminoacidsequencein eachchainis very regularand is mainlybasedon repetitionof three
a m i n oa c i d sT. h el e n g t h so f t h e c h a i n sa n d h y d r o p h o b inca t u r eo f m o s to f t h e R - g r o u pm
s a k et h e
moleculeinsoluble.
Bondingbetweenthe three polypeptide
chainsgivesthe moleculestrength.The
molecules
are furtherassembled
into fibres.Thefibresare flexiblebut cannotbe stretched.
Haemoglobin
Thisis a reddish-purple
respiratorypigmentwhichgivesbloodits red colour.lt combineswith oxygento
form oxyhaemoglobin
whichis a brighterred in colour.lt is a globularproteinand one haemoglobin
moleculeconsists
of four polypeptidechains.Eachchainis associated
with a haemgroupwhichcontains
i r on .

Adulthumanhaemoglobin
consistsof four subunits,two alphachainsand two betachains.With four
polypeptide
chains,haemoglobin
hasa quaternarystructure.The haemgroup is an exampleof a
prosthetic
groupmakinghaemoglobin
a conjugatedprotein.
Oneoxygenmoleculeattachesto eachhaemgroupand thereforewith four haemgroups,one
haemoglobin
moleculecantransportfour molecules
of oxygen.Thefirst moleculeof oxygento attach
doesso with difficultyand as it attachesit distortsthe shapeof the haemoglobin
molecule.This
distortionmakesit easierfor other oxygensto attach.Thesubsequent
three molecules
of oxygenattach
progressively
quickly.
more
Thisprocessis calledco-operative
binding.
The releaseof one of the oxygensfrom oxyhaemoglobin
changes
the shapeof the haemoglobin
moleculeto makereleaseof the otherthreeoxygensincreasingly
easy.
Biochemicaltest for the presenceof proreins(the biuret test)
Thistest dependsuponthe fact that proteinsreactwith alkalinecopper(ll) sulphatesolutionto form a
m a u v e / l i l acco l o u r e dc o m p o u n dc a l l e d ' b i u r e t ,
Procedure:
the food sampleis placedin a test tube.An equalvolumeof biuretreagentis addedto the
,

sample.
lf proteinis present,a mauvecolourdeverops.
Thetest may alsobe carriedout usingseparatesolutions.
Thefood sampleis placedin a test tube.An equalvolume of 5% potassiumhydroxidesolutionis added
a n d m i x e dT. w o d r o p so f L %c o p p e rs u l p h a t e
s o l u t i o na r ea d d e da n d m i x e d .
lf proteinis present,a mauvecolourdevelops.

The role of proteins

Globularproteins
Globularproteinsare found in colloidalsolutionor in cellmembranes.
Theirfunctionsare metabolic
(chemical)'
protein's
A
specificshapeenablesit to'fit'a particular,
specificsubstance
and carryout its
f u n c t i o no n t h a t s u b s t a n coen l y .
Globularproteinsact asenzymes.Thespecificactivesiteon the enzymemoleculefits its substrate,
speedingup a reactioninvolvingthat substrate.
Theyalsoact as carriersin membranes.Someproteinsin membranes
combinewith specificsubstances
and transportthem acrossthe membrane,eitherby facilitateddiffusionor activetransport.

proteins
Globular
alsoactasreceptor
sitesin membranes.
Theseproteins
fit a particular
substance
such
asa hormone
on theoutsideof the membrane.
particular
Thiscombination
triggers
a
reaction
insidethe
cell.Forexample,
insulin
fitsintospecific
receptor
sitesin cellmembranes,
triggering
cellular
reactions
Theyare alsousefulas antibodies.The specificshapeof antibodiesenablesthem to fit specificantigens
when defendingthe bodyagainstdisease.
Haemoglobin
transportsoxygenand myoglobinstoresoxygenin muscles.Bothare globularproteins
Fibrousproteins
Thefunctionof fibrousproteins,dependupontheir insolubility,
strengthand flexible,fibrousnature
ratherthantheir specificshape.Differentfibrousproteinshaveslightlydifferentproperties.
The
proteins
functionsof fibrous
givesflexible
are mainlyrelatedto supportand movement.Collagen
strengthto tendons,bloodvesselwallsand skin.Elastingivesstrengthand elasticityto ligaments.
Keratinis the mainsubstance
of hair,feathersand scales.
Actinand mvosinare neededfor muscle
contraction.

Reference:
ASLevelBiology- Bradfield,
Dodds,Taylor

C{-helix

B-strand

one amino acid

$-pleatedsheet

,r/""',

'/
V:<"t'r:VPePtdebond
"'',2
_,-,,rr,/

hydrogen bond

t,(J
/\-./ -t',:;.;ifi
7
\,JZ
@'J
w/
)'

')

/\
\/ ' /
",r
// i l

'''r.,
,./)
'../1
\"/1,

:/

/Nt/./^

rhis is a ribbonmodelof the

g-helix.
Theactualmolecule

w o u l d b e m o r e ' f i l l e di n '

Figurc l.lll

{&ir\.,r.''
1..
,,/

Seconclarl'stlllctLlrc in protcins

Ihisis a ribbonmodelof thef)-chain

Parallel

p o l y p e p t i d e sw i t h [ ] - c h a i n sc a n b e h e l d t o g e t h e rt o
f o r m p - p l e a t e ds h e e t s w i t h h y d r o g e nb o n d s , w h i c h
t a b i j i s e st h e f 3 _ c h a i n s
lhe o-hclix ancl B-chain.

filobular proteins

Fibrousproteins

Examplcs

h a e n t o g l o b i nc ,n z y m e sa. n t ib o d i c s .
Irans1-rortcrs
in rnctlbrancs.sontc
I t o r r n o n c(se . g .i n s u l i n )

Primarv
structurc

ver-yprcclse,Lrsu:rliv
ntaclcirp ol'a
o l t e n r l a d e u p o 1 ' arepcatrngscclLtcncc
non-rcpcatinsscqLlcllcc
ol' arlino :rcicls ol' antino ircirls.ancltlrc chtrincan bc of
lirrrling a chain that is irlr.'n,avs
thc srrrle v a r y i n gl c n g t h
lr'tt trl lr

i"i"niri,f

n l ' , " , ,: r r l 1 1 H i.n u l r t c r '

..
insolublein u,,a1er

-'----:
r-rsua
I lv nrctabolicallyactive.taking pnr ti u s u a l l rm
v e t a b o l i c a1l1trnrc:tctir,'c.
u'ith a
in chenticalreactiorrs
in iurcllrlc'rrrncl
structuralrolc
i
cclls
------I'able
1.3 A contparist'o
r nl ' g l o b u l a ru n d l i b r . o L pr sf 0 t e l l t s .
Functions

'1
Chapter, Aspects
of biochemistry

Amino acidswith ti{q_.!gtnrBpEpil_co_atgning,\Hr, -COQ_

H*or_AJJ-glorrps*arlbydtephlliE
qp_{_o$g_splublr
rn-yate:=Th9y_m?y_p9lq11o,ly,qd
Lrrrq_n_i-a_b.q-nding-orhy-drogex"
+ld_help!q_fn+_\e,
bq4dingwi!{n 4 p1olgl1gqlggU&.-

HN

NH,

NH,

O.

\"/

I
I
Iil

CH,

j
a s p a r a g r n e glutamine
rE

OH

CH"
tl
H-C -OH

I
I

CHz

T*,
\r'n'
I
?n'
?n'
?"
?*' i $?"

I
I
I

NH,

\./
NH

I
I

I ,t

serine

threonine

rS

t*

i"'

?*'
?*'
IT

COOH

CH"

cHz

CH,

t-j

l_il

argrnrne

lysine

COOH

g l u t a m i ca c i d

aspartic acid

Amino acidswith sidechainsc,o_L91nt!_g*llgj!fU9lq{g!"

o1-with_*_CH,rer-oups:
arehydrophobic,-!qbf"_b_"--r-qgg-y-11blo-op11lln11rnolgqqle.
'itl"y-ay
U. in-u-q'li.d-[]r "a

lq

ld

glycine

?"

T"..
T"

?"

C -CH3

H-

H-C-CH3

1-

I
!

.i
leucine

valrne

a\

CH,

t$

alanrne

C -CH?

H-

H-C-CH3

CH"

methionine

OH

lll
\\

_-/

\J

CH"

t_"

phenylalanine

{
tyrosine

i'-\_/
\/'

",t\
\..'

?*'
tI

?"
ii

tr\,^+^^h^^
L ry P L V P r r O r r

The amino acid cysteine,with 4l -SH $ogg.i1""

its sidechain,is involvedin forming disulphide.
bondswithin a proteinmolecule.

COOH

p r o l i n e( t h ew h o l e
a m i n oa c i d )

histidine

SH
I
I
H-C-H

I
l i l

ti

17

of' a
Figure 1.22 Qttittcrtiarl' strltclure
cr-chaitls are
hlcntoglobit-t ll-ttllccltle'The two
ttl
arlcl bltte' itrld thc trvcl B-chains
itr pr',r1-,1"
shor'r't.t
browt.t atrd tlrltrlgc'