BIOCHEMISTRY 1

2ND CLASS
UNIVERSITY OF ANBAR-COLLOGE OF SCIENCE
BIOLOGY DEPARTMENT
2020-2021

Structures of proteins
Lecture four(4)

Hameed Hussein Ali

Chemistry Department
College of Science 1
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 Learning Objectives
• Different structures of proteins

• Structures of two peptide chains conformations:

alpha helix and beta pleated sheet

• The concept of folding, unfolding and misfolding of

protein

• The deficiency and excess of proteins in human

nutrition

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 Structures of proteins

• Simple proteins are made up of peptide bond

• Conjugated proteins have structures which

incorporate non protein portions called prosthetic
group

• The peptide chains of a particular protein molecule

are folded in the same way. This is known as chain
conformation

• The unique chain conformation of a given protein is

influenced by many week forces (disulfide bridges,
ionic bond, hydrogen bond, etc.) 4
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 Levels of protein structure

●The sequence of a protein is determined by the DNA of

the gene that encodes the protein (or that encodes a
portion of the protein, for multi-subunit proteins).
● A change in the gene's DNA sequence may lead to a
change in the amino acid sequence of the protein. Even
changing just one amino acid in a protein’s sequence can
affect the protein’s overall structure and function.
● To understand how a protein gets its final shape or
conformation, we need to understand the four levels of
protein structure: primary, secondary, tertiary, and
quaternary

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 Primary structure
The simplest level of protein structure, primary
structure is simply the sequence of amino acids in
a polypeptide chain.
The hormone insulin has two polypeptide chains A,
and B. The sequence of the A chain, and the
sequence of the B chain can be considered as an
example for primary structure.

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 Secondary structure
secondary structure, refers to local folded structures that form
within a polypeptide due to interactions between atoms.
The most common types of secondary structures are the α helix
and the β pleated sheet. Both structures are held in shape by
hydrogen bonds, which form between the carbonyl O of one
amino acid and the amino H of another.

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α-Helix

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α-Helix as viewed from one end

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A space feeling model of α- Helix

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 b-Sheet
b-pleated sheet consists of peptide chains
arranged side by side which resembles a
piece of paper folded into many pleats

– Like a helix, the b-sheet uses the full H-

bonding capacity of the polypeptide
backbone

– HOWEVER, H-bonding occurs BETWEEN

neighboring peptide chains, rather than
within one.

– R-groups extend above and below the 13

plane of the sheet

b-Sheet

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b-Sheet

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Pleat of b-Sheet

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 Secondary structures…

• Helices and sheets can be combined in various

ways

• Some proteins have mainly a-helices, some

have mainly b-sheets, but most have both

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 Secondary structure: fibrous proteins

• Water insoluble
• Usually physically tough
• Usually static: provides mechanical support to
individual cells and entire organisms
• E.g., collagen, keratin

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Examples of secondary structure…

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Examples of secondary structure…

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Examples of secondary structure

The collagen triple helix. Left-

handed polypetide helices are
twisted together to form a right-
handed superhelical structure.

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 Tertiary structure
The overall three-dimensional structure of a
polypeptide is called its tertiary structure. The
tertiary structure is primarily due to interactions
between the R groups of the amino acids that
make up the protein.
Important to tertiary structure are hydrophobic
interactions, in which amino acids with nonpolar,
hydrophobic R groups cluster together on the
inside of the protein, leaving hydrophilic amino
acids on the outside to interact with surrounding
water molecules.
Also, Disulfide bonds, covalent linkages between
the sulfur-containing side chains of cysteines, are
much stronger than the other types of bonds that
contribute to tertiary structure 22
• Refers to the complete three dimensional
structure of entire polypeptide. Usually involves
the packing of structural elements (a-helix, b-
pleated sheet, etc.)
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 Tertiary structure: globular proteins

• Structurally complex
• Usually dynamic
• Usually compact (tightly folded), roughly spherical
• Can be water-soluble
– If so, characteristically have hydrophobic interior
and hydrophilic surface
• Can be water-insoluble (e.g., bound to biological
membrane)

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Examples of Tertiary structure…

sperm whale myoglobin

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Examples of Tertiary structure…

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Examples of Tertiary structure…

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Examples of Tertiary structure…

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 Quaternary structure
When multiple polypeptide chain subunits come
together, then the protein attains its quaternary
structure.
An example for quaternary structure is hemoglobin.
The hemoglobin carries oxygen in the blood and is
made up of four subunits, two each of the α and β
types.

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Quaternary structure of proteins

Nitritite reductase E. Coli fumarase

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Human hemoglobin Bacterial methane hydroxylase

 Folding, unfolding and misfolding of protein
• A protein that is folded into its normal physiologically
active chain conformation is in its native state.

• Denaturation occurs when a native protein unfolds

owing to cleavage of disulfide bridges or disruption of the
weak attractive forces. It may be reversible or
irreversible.

• Protein can be denatured by heat, extremes of pH,

certain organic solvents such as alcohol, acetone,
certain solute like urea, or by exposure of the protein to
detergents.
Denatured proteins are usually non-functional
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Model of protein folding

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 Protein misfolding and diseases

• There are at least 15 human diseases in which amyloid

fibers accumulate (as a result of misfolding of proteins).

• Amyloid diseases result in a variety of different clinical

presentations, including Alzheimer’s disease.

• All the proteins involve in these diseases undergo

conformational alteration to a common structure in the
amyloid fibril.

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 Importance of structure:
one example of protein misfolding

• Prion diseases
– “misfolded” protein appears to be causative agent of
many rare degenerative brain diseases in mammals

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 Prions…
• Stanley Prusiner was awarded the 1997 Nobel Prize in
Physiology or Medicine for his work on “prions”

• Prion: name derived from proteinaceous and infectious

– current definition: proteinaceous infectious particle that
lacks nucleic acid
• Prion diseases are invariably fatal neurodegenerative
diseases, including bovine spongiform encephalopathy
(BSE), scrapie of sheep, and Creutzfeldt-Jakob disease
(CJD) of humans.
• ‫البريونات هي السبب في اعتالالت الدماغ االسفنجية المعدية مثل االعتالل الدماغي‬
‫تؤثر على بنية الدماغ او االنسجة العصبية وهي‬.‫االسفنجي البقري وقعاص الغنم‬
.‫امراض قاتلة‬ 35
 Structures of prion proteins

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Taken from: Prusiner, 1998. Proc Natl. Acad. Sci. USA 95:13363-13383.
 Prion diseases…
• May be present as genetic, infectious, or
sporadic disorders

• All involved modification of the prion protein

(PrP)

• Prions are transmissible particles, devoid of

nucleic acid, and apparently composed
exclusively of a modified protein.

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 Prion diseases

• The normal cellular PrP (PrPC) is converted to

modified protein through a posttranslational
process during which it acquires a high b-sheet
content.

• Normal soluble form thus converted to

insoluble form.

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 Collagen Diseases

• Scurvy

• Brittle bone disease

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 Deficiency of Protein in Human

• Growth Failure

• Kwashiorkor ‫سوء التغذية ونقص البروتين‬

• Marasmic Kwashiorkor

• Muscle wasting
Excess of Protein in Human

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Excess of Protein in Human

Stress in kidney

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