IPS1 -Life Cycle of Proteins

Primary protein structure

[Level of Protein Structure and Hierarchy]

sequence of amino acids.

Secondary protein structure

[Level of Protein Structure and Hierarchy]

hydrogen bonding causes formation of alpha helices and beta-pleated sheets.

Tertiary protein structure

[Level of Protein Structure and Hierarchy]
three-dimensional folding due to interactions among side chains.

Quaternary protein structure

[Level of Protein Structure and Hierarchy]

multiple amino acid chains combine to form a functional protein.

True

[T/F]

The primary structure of a protein is the straight chain of amino acids and where any disulfide bonds (-S-S-) connect parts of the chain

disulfide bonds (-S-S-)

[Level of Protein Structure and Hierarchy]

• The primary structure of a protein is the straight chain of amino acids and where any _____connect parts of the chain.

alpha helix

[SECONDARY STRUCTURE OF PROTEINS]

The _____is a common shape in many proteins

alpha helix

[SECONDARY STRUCTURE OF PROTEINS]

____- is held together by hydrogen bonds between parts of the protein chain that are four amino acids apart.

hydrogen bonds

[Type of Bond]

• Alpha helix is held together by_____ between parts of the protein chain that are four amino acids apart.

Keratin

[SECONDARY STRUCTURE OF PROTEINS]

_____ - is mostly made of alpha helices

alpha helices

[SECONDARY STRUCTURE OF PROTEINS]

Keratin is mostly made of ____

Keratin

[SECONDARY STRUCTURE OF PROTEINS]

____-

• Is about 80% alpha helical

• Is a flexible globular protein.

Beta sheet

____- is made of 2 or more sections of amino acids, each 5–10 long.

hydrogen bonds

Beta sheet is held together by ____ between parts of the protein chain that face each other.

Beta sheet

_____- is held together by hydrogen bonds between parts of the protein chain that face each other.

pleated sheet

A _______is due to positioning of the ⍺- carbons of the peptide bond which alternates above and below the plane of the sheet

tertiary structure

[TERTIARY STRUCTURE OF PROTEINS]

____-  

• Is how a protein’s shapes (like helices and sheets) fold into a 3D form.

• This shape is important for the protein to work.

one or more domains

TERTIARY STRUCTURE OF PROTEINS

• A protein can have ____domains, which are parts that fold and work on their own

• Hydrogen bonding

• Hydrophobic interactions

• Eectrostatic interactions

• Van der Waals forces.

Types of Bondings in Tertiary proteins [4]

Quaternary structure

_______-

• Happens when two or more protein chains join to make a bigger protein

• They stick together using the same weak forces that shape single proteins

oligomeric proteins

Proteins with QUATERNARY STRUCTURE are called ____

• homooligomers

• heterooligomers

[QUATERNARY STRUCTURE]

• If the chains are all the same, they’re____

• If the chains are different, they’re____

Protein denaturation

____- happens when proteins lose their shape because of heat, strong acids or bases, solvents, mixing, detergents, or heavy metals like lea

Protein denaturation

This breaks the weak bonds that keep the protein’s shape but doesn’t break the links between amino acids.

True

[T/F] 

In Protein Denaturation

• When the shape is lost, the inside parts of the protein are exposed, making proteins stick together.

True

[T/F]

In rare cases, a denatured protein can return to its original shape if the cause of denaturation is removed

True

[T/F]

Most proteins stay permanently damaged and do not return to their normal shape.

Denatured proteins

[Type of Protein]

____- are usually insoluble and may form solid clumps (precipitate) in solution

Feature	PrPC (Normal)	PrPSc (Abnormal/Disease)
Full Name	Cellular prion protein	Scrapie prion protein
Structure (Primary)	Same amino acid sequence as PrPSc	Same amino acid sequence as PrPC
Structure (Secondary)	Mostly alpha helices	Mostly beta sheets
Solubility	Soluble	Insoluble (except in strong solvents)
Digestion by Proteases	Easily digested	Resistant to digestion
Gene	PRNP on chromosome 20 (in humans)	Same gene
Behavior	Normal function	Converts PrPC into more PrPSc
Aggregation	Does not aggregate	Forms harmful aggregates

PATHOLOGIC CONSEQUENCES OF PROTEIN CONFORMATION PERTURBATION

Transmissible Spongiform Encephalopathies (TSEs

Prion Disease is aka ___

Prion Disease (Transmissible Spongiform Encephalopathies (TSEs) ) 

These are fatal brain diseases that cause  

• Sponge-like holes in brain tissue

• Brain cell damage and loss

• Build-up of harmful, insoluble protein clumps

True

[T/F]

Prion Disease (Transmissible Spongiform Encephalopathies (TSEs) ) can affect both humans and animals.

• Creutzfeldt-Jakob Disease (CJD) – in humans

• Scrapie – in sheep 

• Mad Cow Disease (BSE) – in cattle

Examples of Prion Disease (Transmissible Spongiform Encephalopathies (TSEs)) [2]

Alzheimer’s Disease

These brain problems are linked to the misfolding of beta-amyloid proteins.

beta-amyloid

[Alzheimer’s Disease]

Normally, _____ [alpha / beta] amyloidis soluble and has mostly alpha-helix structure.

Alzheimer’s Disease

[Type of Disease]

It changes to a beta-sheet structure, which makes it stick together and form clumps.

apolipoprotein E (ApoE)

[Alzheimer’s Disease]

A protein called _____may help trigger this harmful shape change.

Beta-Thalassemia

___- is mostly seen in people who experience nosebleeds — “nanonosebleed”

Beta-Thalassemia

In _______ 

• Genetic problems can affect how certain hemoglobin subunits are made.

Beta-Thalassemia

One cause is the lack of a helper protein called AHSP (alphahemoglobin stabilizing protein)

AHSP (alphahemoglobin stabilizing protein)

In Beta-Thalassemia

• One cause is the lack of a helper protein called____

free alphahemoglobin

In Beta-Thalassemia

• Without AHSP (alphahemoglobin stabilizing protein), _____chains clump together.

free alphahemoglobin chains clumps

In Beta-Thalassemia

• These clumps are toxic and can damage developing red blood cells.

Enzyme Test	Disease / Condition	Primary Organ / System
Creatine Kinase (CK)	Heart attack, muscular dystrophy, muscle injury	Heart & Muscle
Alanine Aminotransferase (ALT)	Hepatitis, cirrhosis, liver damage	Liver
Aspartate Aminotransferase (AST)	Liver damage, heart attack, muscle injury	Liver & Heart
Alkaline Phosphatase (ALP)	Blocked bile ducts, hepatitis, Paget’s disease	Liver & Bone
Lactate Dehydrogenase (LDH)	General tissue damage; also used to monitor some cancers	Various Tissues & Cancer
Amylase & Lipase	Pancreatitis, pancreatic cancer	Pancreas

CLINICAL USE OF ENZYMES