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AP Biology

Structureof proteins

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AP Biology

Proteins

Most structurally & functionally diversegroup of biomolecules

Function:

involved in almost everything enzymes

structure (keratin, collagen)

carriers & transport (membrane channels)

receptors & binding (defense) contraction (actin & myosin)

signaling (hormones)

storage (bean seed proteins)

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AP Biology

Proteins

Structure: monomer = amino acids

20 different amino acids

polymer = polypeptide protein can be 1 or more polypeptide chains

folded & bonded together

large & complex molecules

complex 3-D shape

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AP Biology

Amino acids

Structure: central carbon

amino group

carboxyl group (acid) R group (side chain) variable group

confers unique

chemical propertiesof the amino acid N

H

H

H

|C|

COH||

O

R

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Types of Amino Acids based on

side-chain chemical character :

Non-Polar (8 AAs) :- hydrocarbon (5 AAs) : Ala, Val,

Leu, Ile, Pro

- aromatic (2 AAs) : Phe, Trp

- thiol ether(1 AA) : Met

Flexible (1 AA) :

- gly flexible because it has no

side chain

Polar (11 AAs) :

- alcohols (3 AAs) :Ser, Thr, Tyr- thiol (1 AA) : Cys

- amides (2 AAs) : Asn, Gln

- acids (2 AAs) : Asp. Glu

- bases (3 AAs) : Lys, Arg, His

http://www.bio.mtu.edu/campbell/hydrocar.htmhttp://www.bio.mtu.edu/campbell/aromatic.htmhttp://www.bio.mtu.edu/campbell/thiol.htmhttp://www.bio.mtu.edu/campbell/flexible.htmhttp://www.bio.mtu.edu/campbell/alcohol.htmhttp://www.bio.mtu.edu/campbell/cysthiol.htmhttp://www.bio.mtu.edu/campbell/amide1.htmhttp://www.bio.mtu.edu/campbell/acid1.htmhttp://www.bio.mtu.edu/campbell/bases1.htmhttp://www.bio.mtu.edu/campbell/bases1.htmhttp://www.bio.mtu.edu/campbell/bases1.htmhttp://www.bio.mtu.edu/campbell/bases1.htmhttp://www.bio.mtu.edu/campbell/bases1.htmhttp://www.bio.mtu.edu/campbell/acid1.htmhttp://www.bio.mtu.edu/campbell/acid1.htmhttp://www.bio.mtu.edu/campbell/acid1.htmhttp://www.bio.mtu.edu/campbell/acid1.htmhttp://www.bio.mtu.edu/campbell/amide1.htmhttp://www.bio.mtu.edu/campbell/amide1.htmhttp://www.bio.mtu.edu/campbell/amide1.htmhttp://www.bio.mtu.edu/campbell/amide1.htmhttp://www.bio.mtu.edu/campbell/cysthiol.htmhttp://www.bio.mtu.edu/campbell/cysthiol.htmhttp://www.bio.mtu.edu/campbell/cysthiol.htmhttp://www.bio.mtu.edu/campbell/cysthiol.htmhttp://www.bio.mtu.edu/campbell/alcohol.htmhttp://www.bio.mtu.edu/campbell/flexible.htmhttp://www.bio.mtu.edu/campbell/thiol.htmhttp://www.bio.mtu.edu/campbell/thiol.htmhttp://www.bio.mtu.edu/campbell/thiol.htmhttp://www.bio.mtu.edu/campbell/thiol.htmhttp://www.bio.mtu.edu/campbell/aromatic.htmhttp://www.bio.mtu.edu/campbell/aromatic.htmhttp://www.bio.mtu.edu/campbell/aromatic.htmhttp://www.bio.mtu.edu/campbell/aromatic.htmhttp://www.bio.mtu.edu/campbell/hydrocar.htm

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AP Biology

Nonpolar amino acids

nonpolar & hydrophobic

Why are these nonpolar & hydrophobic?

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AP Biology

Polar amino acids

polar or charged & hydrophilic

Why are these polar & hydrophillic?

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Sulfur containing amino acids

Disulfide bridges cysteines form cross links

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AP Biology

Building proteins

Peptide bonds: dehydration synthesis linking NH2 of 1 amino acid to

COOH of another

CN bond

peptidebond

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AP Biology

Building proteins

Polypeptide chains N-terminal = NH2 end

C-terminal = COOH end

repeated sequence (N-C-C) is thepolypeptide backbone

grow in one direction

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AP Biology

Protein structure & function

function depends on structure all starts with the

order of amino acids what determines that order of

amino acids?

lysozyme: enzyme in tears & mucus that kills bacteria

the 10 glycolytic enzymes

used to breakdown glucoseto make ATP

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AP Biology

Protein structure is broken down into fourlevels:

primary structure

secondary structure

tertiary structure

quaternary structure

Protein structure

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Primary (1) structure

Orderof amino acids in chain amino acid sequence

determined by DNA

slight change in amino acidsequence can affect proteinsstructure & its function

even just one amino acid change

can make all the difference!

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AP BiologyPeptides = Mini-Proteins

Primary (1) structure

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AP Biology

Sickle cell anemia

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AP Biology

Secondary (2) structure

Local folding Folding along

short sections of

polypeptide

interaction between

adjacent amino

acids

H bonds between

R groups

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AP Biology

Tertiary (3) structure

Whole molecule folding determined by interactions

between R groups

hydrophobic

interactionseffect of water

in cell

anchored by

disulfide bridges(H & ionic bonds)

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AP Biology

Tertiary (3) structure

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Quaternary (4) structure

Joins together more than 1 polypeptide chain only then is it a functional protein

hemoglobin

collagen =

skin & tendons

Lets go to the video tape!(play movie here)

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AP Biology

Quaternary (4) structure

Quaternary (4) structure is the arrangement ofseparate polypeptide chains (subunits) relative toeach otherjoins together more than 1polypeptide chain. These chains may be identicalto each other, or different from each other. Only

then is it a functional protein We classify proteins into 2 major groups

according to tertiary (3) and quarternary (4)structure:

- fibrous- globular.

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AP Biology

In general, fibrous proteins are :- built up from a single element of secondary structure

- insoluble in water (lots of hydrophobic residues)

- involved in structural roles within the cell

Fibrous proteins

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AP Biology

Right-hand

Left-hand

a-keratin - the protein of hair

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Hair Wool Nails Claws

Quills Horn Hooves Outer layer of skin

a-keratin

Disulfide bondsstabilize. Toughness depends

on amount ofdisulfides

Rhinoceros horn,18% of residues areCys in disulfides.

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AP Biology

Produced by insects and

spiders. High tensile strength, but

flexible Mostly close-packed b-

sheets

Rich in Ala and Gly(alternating why?)

No covalent bondsbetween strands orsheets.

Extensive H-bonding andvan der Waalsinteractions for strength.

Silk Fibroin

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AP Biology

Left-hand single helix, 3residues/turn

1/3 Gly, 1/5 Pro or Hyp Triplet Gly-X-Pro (or

Gly-X-Hyp) repeats Supertwisted coiled coilis right-handed, madeof 3 left-handed a-chains

Non-standard covalentx-links.

LH RH

Collagen

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AP Biology

Tendons Cartilage

Bone matrix Cornea of the eye

Lungs

Collagen

> 30 structural variantsof collagen in a mammal

Different tissues havedifferent collagens.

Diseases of collagenabnormalities Ehler-Danlossyndrome

Osteogenesisimperfecta.

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AP Biology

Compact Made up of regions ofa-helix, b-sheets, b-

turns, and others as

well Stability primarily

results fromhydrophobic core; also

H-bonding.

Globular proteins

9/16/05

Carbonic anhydrase

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AP Biology

A small protein (153 aas, 16.7 kD) Contains a heme prosthetic group

Stores oxygen in muscle cells It is mostly a-helix (78% of its aas are in

the 8 segments, from 7 to 23 aas long),linked by turns (some of them b) Much of its stability comes from hydrophobic

interactions

Myoglobin, a globular protein

9/16/05

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AP Biology

Myoglobin structure

Ball-and-stick: Ribbon:

Ribbon diagram shows backbone conformation.

.

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AP Biology

Domains

Troponin C.Note : 1 polypeptide chain!

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AP Biology

Domains

9/16/05Fig. 4-19

Domains are usually > 100 aasDomains are often functional and comprise acontiguous segment of the full protein

Domain structure is thought to reflect the

evolutionary fusion of functional elements tocreate novel new proteins

Domains are stable, self-folding

substructures

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AP Biology

Multimers are assembled from multiplepolypeptide chains.

Have we learned about any multimers yet? One of them: hemoglobin.

Multimers

9/16/05

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AP Biology

Protein structure (review)

1

2

3

4

aa sequencepeptide bonds

R groups

H bonds

R groupshydrophobic interactions,

disulfide bridges

determinedby DNA

multiplepolypeptideshydrophobic

interactions

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AP Biology

Protein Folding

Tujuan folding :

Untuk menghasilkan suatu bentuk unik yang

compatibel dengan fungsi biologis spesifik

Untuk memperoleh bentuk yang stabil secara

kimia

The driving force for protein folding is

provided by water

Protein folding is a bit like a drop of oil inwater

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AP Biology

Chaperonin proteins

Guide protein folding provide shelter for folding polypeptides

keep the new protein segregated from

cytoplasmic influences

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AP Biology

Protein models

Protein structure visualized by X-ray crystallography

extrapolating from amino acid sequence

computer modelling

lysozyme

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Denature a protein

Disrupt 3 structure pH salt

temperature

unravel ordenature protein

disrupts H bonds, ionic bonds &

disulfide bridges

Some proteins can

return to theirfunctional shape

after denaturation,

many cannot

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AP Biology

Homologous Proteins

have similar function and similar AA sequence aswell as 3D shape

Invariant AAs are involved in function or bonding

critical to the protein's shape

Variable AAs are only parts of the protein'sframework

analyze the AA sequences of the same protein from

different organisms

example is the electron carrying protein of

mitochondria called Cytochrome c which has a

bound heme-Fe so it has a red-orange color like

hemoglobin

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AP Biology

Cytochrome C

Structural model of Cytochrome C showing

a few of its invariant amino acids

Since Cytochrome c

appears to be required

for survival of

eukaryotic organisms,

change in its amino

acid sequence, whichreflects change in its

gene, can be used to

measure change in

species during

evolution.

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AP Biology

AMINO ACID SEQUENCE OF CYTOCHROME C

These invariant AA are absolutely required for

functionality of cytochrome c

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AP Biology

PHYLOGENETIC TREE OF SPECIES BASED ON THE

AMINO ACID SEQUENCE OF CYTOCHROME C

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AP Biology

SIMILAR FUNCTION - DIFFERENT SEQUENCE

Cth: Dehydrogenases are enzymes transferring electrons from a

reduced substrate to NAD+ -- a cellular electron carrier.

3 different dehydrogenases (alcohol dehydrogenase, lactate

dehydrogenase, and glyceraldehyde-phosphate dehydrogenase)

which all use NAD+ as an electron acceptor, but use different

metabolites as the reduced substrate which donates the electrons

to NAD+ making it into NADH:

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AP Biology

ENZYMES WITH THE SAME 3-D

SHAPE BUT DIFFERENT FUNCTIONS

These enzymes have no similarity in AA sequence

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Lets build some

Proteins!