Structure of proteins

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Proteins Most structurally & functionally diverse

group 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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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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Amino acids Structure:

central carbon amino group carboxyl group (acid) R group (side chain)

variable group confers unique

chemical properties of the amino acid

H O H | || N C COH | H 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
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Nonpolar amino acids nonpolar & hydrophobic

Why are these nonpolar & hydrophobic?

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Polar amino acids polar or charged & hydrophilic

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Why are these polar & hydrophillic?

Sulfur containing amino acids Disulfide bridges

cysteines form cross links

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Building proteins Peptide bonds: dehydration synthesis

linking NH2 of 1 amino acid to COOH of another CN bond

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peptide bond

Building proteins Polypeptide chains

N-terminal = NH2 end C-terminal = COOH end repeated sequence (N-C-C) is the polypeptide backbone

grow in one direction

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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

AP Biology the 10 glycolytic enzymes used to breakdown glucose to make ATP

Protein structure
Protein structure is broken down into four levels: primary structure secondary structure

tertiary structure
quaternary structure

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Primary (1) structure Order of amino acids in chain

amino acid sequence determined by DNA slight change in amino acid sequence can affect proteins structure & its function

even just one amino acid change

can make all the difference!

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Primary (1) structure

Peptides = Mini-Proteins AP Biology

Sickle cell anemia

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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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Tertiary (3) structure

Whole molecule folding

determined by interactions between R groups hydrophobic interactions effect of water in cell anchored by disulfide bridges (H & ionic bonds)

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Tertiary (3) structure

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Quaternary (4) structure

Joins together more than 1 polypeptide chain

only then is it a functional protein

collagen = skin & tendons

Lets go to the video tape! AP Biology

(play movie here)

hemoglobin

Quaternary (4) structure

Quaternary (4) structure is the arrangement of
separate polypeptide chains (subunits) relative to each other joins together more than 1 polypeptide chain. These chains may be identical to 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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Fibrous proteins

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
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a-keratin - the protein of hair

Right-hand Left-hand

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a-keratin

Hair Wool Nails Claws Quills Horn Hooves Outer layer of skin

Disulfide bonds

stabilize. Toughness depends on amount of disulfides Rhinoceros horn, 18% of residues are Cys in disulfides.

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Silk Fibroin
Produced by insects and
spiders. High tensile strength, but flexible Mostly close-packed bsheets Rich in Ala and Gly (alternating why?) No covalent bonds between strands or sheets. Extensive H-bonding and van der Waals interactions for strength.

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Collagen

Left-hand single helix, 3

residues/turn 1/3 Gly, 1/5 Pro or Hyp Triplet Gly-X-Pro (or Gly-X-Hyp) repeats Supertwisted coiled coil is right-handed, made of 3 left-handed achains Non-standard covalent x-links.

LH
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RH

Collagen

Tendons Cartilage Bone matrix Cornea of the eye Lungs

> 30 structural variants

of collagen in a mammal Different tissues have different collagens. Diseases of collagen abnormalities

Ehler-Danlos syndrome Osteogenesis imperfecta.

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Globular proteins

Compact Made up of regions of

a-helix, b-sheets, bturns, and others as well Stability primarily results from hydrophobic core; also H-bonding.

Carbonic anhydrase
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9/16/05

Myoglobin, a globular protein

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

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9/16/05

Myoglobin structure
Ball-and-stick: Ribbon:

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Ribbon diagram shows backbone conformation. .

Domains

Troponin C. Note : 1 polypeptide chain!

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Domains
Domains

are usually > 100 aas Domains are often functional and comprise a contiguous segment of the full protein Domain structure is thought to reflect the evolutionary fusion of functional elements to create novel new proteins Domains are stable, self-folding substructures

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Fig. 4-19

9/16/05

Multimers

Multimers are assembled from multiple

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

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9/16/05

Protein structure (review)

R groups hydrophobic interactions, disulfide bridges

1
aa sequence peptide bonds

multiple polypeptides hydrophobic interactions

determined by DNA
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2
R groups H bonds

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 in water

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Chaperonin proteins
Guide protein folding

provide shelter for folding polypeptides keep the new protein segregated from cytoplasmic influences

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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 temperature

salt

unravel or denature protein

disrupts H bonds, ionic bonds & disulfide bridges

Some proteins can

return to their functional shape after denaturation, many cannot
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Homologous Proteins
have similar function and similar AA sequence as well 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's framework 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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Cytochrome C
Since Cytochrome c appears to be required for survival of eukaryotic organisms, change in its amino acid sequence, which reflects change in its gene, can be used to measure change in species during evolution.

Structural model of Cytochrome C showing a few of its invariant amino acids

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AMINO ACID SEQUENCE OF CYTOCHROME C

These invariant AA are absolutely required for functionality of cytochrome c

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PHYLOGENETIC TREE OF SPECIES BASED ON THE AMINO ACID SEQUENCE OF CYTOCHROME C

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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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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!

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