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Protein Structure

From: Protein Data Bank PDB ID: 1B0EKalus, W., Zweckstetter, M., Renner, C., Sanchez, Y., Georgescu, J., Grol, M., Demuth, D., Schumacher, R., Dony, C., Lang, K., Holak, T. A.: structure of the IGF-binding

domain of the insulin-like growth factor-binding protein-5 (IGFBP-5): implications for IGF and IGF-I receptor interactions.EMBO J17pp. 6558 (1998)

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Functions

Diverse functions related to structure Structural components of cells

Motor proteins

Enzymes

Antibodies

Hormones Hemoglobin/myoglobin

Transport proteins in blood

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Structure

Amino acids

Amino group(NH2)

Carboxyl group

(COOH)

From: Elliott, WH. Elliott, DC. (1997) Biochemistry

and Molecular Biology. Oxford: Oxford University

Press. p23

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Amino acids

20 amino acids makeup protein

8 essential aminoacids

9 in infant (histidine)

Dipolar +ve end (NH3

+)

-ve end (COO-)

From: Elliott, WH. Elliott, DC. (1997) Biochemistry

and Molecular Biology. Oxford: Oxford UniversityPress. p23

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Protein structure - bonding

5 bonds or forces determine structure

Peptide bond Hydrogen bond

Disulfide bond

Ionic bond Hydrophobic force

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Peptide bond

Peptide bond joinsamino acids

Bond at both ends Increases range of

possible proteins 2 peptides can result

from bonding of 2

amino acids 1.0 x 1026 peptides can

be formed from 20amino acids

From: Elliott, WH. Elliott, DC. (1997) Biochemistry

and Molecular Biology. Oxford: Oxford University

Press. p23

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Primary protein structure

Linear sequence of

amino acids formsprimary structure

Sequence essential for

proper physiologicalfunction

Bettelheim & March (1990) Introduction

to Organic & Biochemistry

(International Edition) Philadelphia:Saunders College Publishing, p299

Primary structure of insulin

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Sickle cell anemia

Replacement of

single glutamine

with valine in one

polypeptide chain

of hemoglobinalters structure

and function Bettelheim & March (1990) Introduction to Organic & Biochemistry(International Edition) Philadelphia: Saunders College Publishing, p301

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Secondary protein structure

Peptide chains fold into secondary

structures: - helix

- pleated sheet

Random coil

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- helix

Shapemaintained by

hydrogen bondsbetween C=Oand N-H groupsin backbone

R groupsdirectedoutward from

coil

From: Elliott, WH. Elliott, DC. (1997) Biochemistry and Molecular

Biology. Oxford: Oxford University Press. p28

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- pleated sheet

Structuremaintained by

hydrogen bondsbetween C=O andN-H groups in

backbone R groups directed

above and below

backboneFrom: Elliott, WH. Elliott, DC. (1997) Biochemistry and Molecular

Biology. Oxford: Oxford University Press. p29

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Random coil Not really random

structure, just non-repeating

Random coil has fixedstructure within a givenprotein

Commonly calledconnecting loop region

Structure determinedby bonding of sidechains (i.e. notnecessarily hydrogenbonds)

From: Elliott, WH. Elliott, DC. (1997) Biochemistry

and Molecular Biology. Oxford: Oxford University

Press. p27

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Tertiary protein structure

Secondary structures fold and pack

together to form tertiary structure

Usually globular shape

Tertiary structure stabilised by bondsbetween R groups (i.e. sidechains)

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H bonds weak

allowing to be

broken and

reformed easily

Allows structural

change produces

functional

molecules

Hydrogen bond

Tertiary structure - H bond

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Tertiary structure - disulfidebond

Covalent bondbetween sulfuratoms on twocysteine amino

acids

From: Elliott, WH. Elliott, DC. (1997) Biochemistry

and Molecular Biology. Oxford: Oxford University

Press. p32

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Tertiary structure - ionic bond

Ions on Rgroups formsalt bridgesthrough ionic

bonds

From: Summerlin, LR. (1981) Chemistry for the Life Sciences. New

York: Random House, p459

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Tertiary structure -hydrophobic forces

Close attraction of non-

polar R groups through

dispersion forces

Very weak but collective

interactions over large

area stabilise structure

Repel polar and charged

molecules/particles Bettelheim & March (1990) Introduction to Organic & Biochemistry(International Edition) Philadelphia: Saunders College Publishing, p302

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Quaternary protein structure

Arrangement of

multiple tertiary

structures into single

functional complex

Allows for changes in

structure/function in

response to chemical

stimuliFrom: Elliott, WH. Elliott, DC. (1997) Biochemistry and

Molecular Biology. Oxford: Oxford University Press. p27