Protein Structure

©1999 Timothy G. Standish

Protein StructureProtein Structure

Timothy G. Standish, Ph. D.

©1999 Timothy G. Standish

S E C O N D B A S E

A

GGUGGCGGAGGG

Gly*

AGUAGCAGAAGG

Arg

G

CGUCGCCGACGG

Arg

GUGUUGCUGAUGG

C

GAUGACGAAGAG

AAUAACAAAAAG

Glu

CAUCACCAACAG

AUAUUACUAAUAG

Stop

Tyr

GUUGUCGUAGUG

Val

AUUAUCAUAAUG start

Ile

CUUCUCCUACUG

Leu

UUUUUUCUUAUUG

Leu

Phe

Met/

GCUGCCGCAGCG

Ala

ACUACCACAACG

Thr

CCUCCCCCACCG

Pro

CUCUUCCUCAUCG

Ser

UCAG

U

UCAG

UCAG

UCAG

Gln†

His

Trp

Cys THIRD

BASE

FIRST

BASE

The Genetic CodeThe Genetic Code

Asp

Lys

Asn†

Stop

Ser

Neutral Non-polarPolarBasicAcidic

†Have aminegroups

*Listed as non-polar bysome texts

©1999 Timothy G. Standish

Polar

BasicAcid

?

AcidAmine

Different Amino Acid ClassesDifferent Amino Acid Classes

OH

O

H

H2N

C

C

R

Generic

Non-polar

C

C

C

OH

H

H

O

H+N

H

H2N

CNH

C

C

Histidine

H

H2N

C

C

H

H

O

OH

O

C

OH

C

Aspartic acid

C

C

C

OH

H

H

O

HS

H

H2N

Cysteine

OH

H

H

O

H

H

H2N

C

C

C

Alanine

©1999 Timothy G. Standish

Non-PolarNon-PolarAmino AcidsAmino AcidsOH

O

H

H2N

C

C

H

Glycine

Leucine

OH

O

H

H2N

C

C

H3C CH3

H

C H

H

C

Methionine

OH

O

H

H2N

C

C

H3C

H

H

C H

H

C

SAlanine

OH

H

H

O

H

H

H2N

C

C

C

Valine

OH

O

H

H2N

C

C

H3C CH3

H

C

Phenylalanine

OH

H

H

O

H

H2N

C

C

C

Tryptophan

OH

O

H

H2N

C

C

NH

H

C

HIsoleucine

OH

O

H

H2N

C

C

H3C H

H

C H

H3C

C

Proline

OH

O

H

H2N+

C

CH2C

CH2H2C

©1999 Timothy G. Standish

Polar Amino AcidsPolar Amino Acids

Cysteine

C

C

C

OH

H

H

O

HS

H

H2N

Serine

OH

O

H

H2N

C

C

HO CH3

H

C

Threonine

OH

O

H

H2N

C

C

H

H

C OH

H

C

H

Tyrosine

HO

H

H

O

H

H2N

C

C

C

OH

Asparagine

H

H2N

C

C

H

H

O

OH

O

C

NH2

C

Glutamine

H

H2N

C

C

H

H

O

OH

O

C

NH2

C

C

H

H

©1999 Timothy G. Standish

Acidic Amino AcidsAcidic Amino Acids

Aspartic acid

H

H2N

C

C

H

H

O

OH

O

C

OH

C

Glutamicacid

H

H2N

C

C

H

H

O

OH

O

C

OH

C

C

H

H

©1999 Timothy G. Standish

Basic Amino AcidsBasic Amino AcidsHistidine

C

C

C

OH

H

H

O

H+N

H

H2N

CNH

C

C

Lysine

OH

O

H

H2N

C

C

+H3N

H

H C H

H

C

C

H

H H

H

C

Arginine

OH

O

H

H2N

C

C

H

H C H

H

C

C

H

H

H

N+H2N

NH2

C

©1999 Timothy G. Standish

Levels Of Protein OrganizationLevels Of Protein Organization Primary Structure - The sequence of amino acids in the

protein Secondary Structure - The formation of helices and

pleated sheets due to hydrogen bonding between the peptide backbone

Tertiary Structure - Folding of helices and sheets influenced by R groups

Quaternary Structure - The association of more than one polypeptide into a protein complex influenced by R groups

©1999 Timothy G. Standish

Levels Of Protein OrganizationLevels Of Protein OrganizationPrimary StructurePrimary Structure

Met-Gly-Ala-Pro-His-Ile-Asp-Glu-Met-Ser-Thr-...

Glyceraldehyde-3-Phosphate Glyceraldehyde-3-Phosphate Dehydrogenase Primary StructureDehydrogenase Primary Structure The Mycoplasma genitalium G-3P dehydrogenase

protein sequence: MAAKNRTIKV AINGFGRIGR LVFRSLLSKA NVEVVAINDL

TQPEVLAHLL KYDSAHGELK RKITVKQNIL QIDRKKVYVF SEKDPQNLPW DEHDIDVVIE STGRFVSEEG ASLHLKAGAK RVIISAPAKE KTIRTVVYNV NHKTISSDDK IISAASCTTN CLAPLVHVLE KNFGIVYGTM LTVHAYTADQ RLQDAPHNDL RRARAAAVNI VPTTTGAAKA IGLVVPEANG KLNGMSLRVP VLTGSIVELS VVLEKSPSVE QVNQAMKRFA SASFKYCEDP IVSSDVVSSE YGSIFDSKLT NIVEVDGMKL YKVYAWYDNE SSYVHQLVRV VSYCAKL

©1999 Timothy G. Standish

Protein Secondary StructureProtein Secondary Structure

The peptide backbone of DNA has areas of positive charge and negative charge

These areas can interact with one another to form hydrogen bonds

The result of these hydrogen bonds are two types of structures: helices pleated sheets

©1999 Timothy G. Standish

+-

Protein Secondary Structure:Protein Secondary Structure: Helix Helix

C

O

OHCN

H

HH

C

HO H

C

H

O

CN

H

HH

C

H H

CHN

C

OC

HN

OC

COC

HN

C HN

COC

OCO

C

OC

HN

H

N

CHN

©1999 Timothy G. Standish

+-

Protein Secondary Structure:Protein Secondary Structure: Helix Helix

C

O

OHCN

H

HH

C

HO H

C

H

O

CN

H

HH

C

H H

CHN

C

OC

HN

OC

COC

HN

C HN

COC

OCO

C

OC

HN

H

N

CHN

©1999 Timothy G. Standish

Protein Secondary Structure:Protein Secondary Structure: Helix Helix

R

RR

R

R

R

R

RR

R R

RR

R

R groups stick out from the helix influencing higher levels of protein organization

©1999 Timothy G. Standish

Yeast Cytochrome C Yeast Cytochrome C Oxidase Subunit IV LeaderOxidase Subunit IV Leader

MLSLRQSIRFFKPATRTLCSSRYLL

RY

PL

T

CS

R

L

S

T

I

KP

R

F

A

F

M

RQ

L

L

S

S

This leader sequence probably forms an helix

This would localize specific classes of amino acids in specific parts of the helix

There are about 3.6 amino acids per turn of the helix with a rise of 0.54 nm per turn

First 12 residues are sufficient for transport to the mitochondria

Neutral Non-polarPolarBasicAcidic

©1999 Timothy G. Standish

Protein Secondary Structure:Protein Secondary Structure: Pleated Sheet Pleated Sheet

NH

C

O

C

H

CC

N

O

NH

C

O

C

H

CC

N

O

NH

C

O

C

H

CC

N

O

NH

C

O

C

H

CC

N

O

NH

C

OC

H

CCN

ONH

C

OC

H

CCN

ONH

C

OC

H

CCN

ONH

C

OC

H

CCN

O

©1999 Timothy G. Standish

Protein Secondary Structure:Protein Secondary Structure: Pleated Sheet Pleated Sheet

NH

C

O

C

H

CC

N

O

NH

C

O

C

H

CC

N

O

NH

C

O

C

H

CC

N

O

NH

C

O

C

H

CC

N

O

NH

C

O

C

H

CC

N

O

NH

C

O

C

H

CC

N

O

NH

C

O

C

H

CC

N

O

NH

C

O

C

H

CC

N

O

NH

C

OC

H

CCN

ONH

C

OC

H

CCN

ONH

C

OC

H

CCN

ONH

C

OC

H

CCN

O

©1999 Timothy G. Standish

Levels Of Protein OrganizationLevels Of Protein OrganizationTertiary StructureTertiary Structure

Tertiary structure results from the folding of helices and pleated sheets

Factors influencing tertiary structure include: Hydrophobic/hydrophilic interactions Hydrogen bonding Disulfide linkages Folding by chaperone proteins

©1999 Timothy G. Standish

G-3-P DehydrogenaseG-3-P DehydrogenaseTertiary StructureTertiary Structure

Picture source: SWISS-PROT

©1999 Timothy G. Standish

Levels Of Protein OrganizationLevels Of Protein OrganizationQuaternary StructureQuaternary Structure

Quaternary structure results from the interaction of independent polypeptide chains

Factors influencing quaternary structure include: Hydrophobic/hydrophilic interactions Hydrogen bonding The shape and charge distribution on associating

polypeptides

©1999 Timothy G. Standish

G-3-P DehydrogenaseG-3-P Dehydrogenasefrom Bacillus stearothermophilusfrom Bacillus stearothermophilus

Skarzynski, T., Moody, P. C. E., Wonacott, A. J.: Structure of Holo-Glyceraldehyde-3-Phosphate Dehydrogenase from Bacillus Stearothermophilus at 1.8 Angstroms Resolution. J.Mol.Biol. 193 pp. 171 (1987) Picture source: SWISS-PROT

©1999 Timothy G. Standish

The Globin Gene FamilyThe Globin Gene Family Globin genes code for the

protein portion of hemoglobin In adults, hemoglobin is made

up of an iron containing heme molecule surrounded by 4 globin proteins: 2 globins and 2 globins

During development, different globin genes are expressed which alter the oxygen affinity of embryonic and fetal hemoglobin

Fe

©1999 Timothy G. Standish

HaemoglobinHaemoglobin

Luisi, B., Shibayama, N.: Structure of Haemoglobin in the Deoxy Quaternary State with Ligand Bound at the Alpha Haems. J.Mol.Biol. 206 pp. 723 (1989)

Picture source: SWISS-PROT

©1999 Timothy G. Standish