Module 3: Proteins

Date Created @September 18, 2023 4:12 PM

Unit 1: Proteins: What do they do, how are they made, what do
they look like?
Functions:

Transport and signalling - move substances across the cell membrane

Movement and Structure - important for moving individual cells or moving large
cargo or molecules within cells.

Enzymes - to speed up to the synthesis of carbohydrates.

Defense - involved in defense mechanism in our body, made by specialized immune

cells and serve the role of antibodies that can destroy disease-causing viruses and
bacteria.

Structures:
Protein structural differences relate to their functions.
#1. TATA-box binding protein, which interacts with DNA molecule due to a groove in the
protein.
#2. Porin proteins are important for the transport of water, they have a structural
hydrophilic pore.

Unit 2: Synthesis: from DNA to Primary Protein Structures

The genetic information for every protein is encoded from the DNA of the cell.
First Step: transcribe information into RNA, which serves as the template for synthesis
of a polypeptide.

Prokaryotic Cell Eukaryotic Cell

closely linlked with translation of the primary RNA transcript is processed
RNA into proteins by ribosomes to mRNA and transported into the

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 cytoplasm where it is translate into
the protein by the ribosomes.

The nucleus contains most of the genes in eukaryotic cells.

The double-membraned nucleus envelope surrounds the nucleus and encloses the
genetic material, separating from the cytoplasm.

The appropriate segment of DNA is read and transcribed into RNA within the
nucleus before protein synthesis occurs.

The double membrane of the nuclear envelope has pore complexes that allows for
material to flow in and out of the nucleus.

most ribosomal RNA are made in the nucleolus, they bind to proteins to form
ribosomal subunits. Then they get exported to the cytoplasm.

Nuclear pore complexes play a crucial role in transporting transcribed RNA out of
the nucleus and importing building blocks of DNA and RNA into the nucleus.

They facilitate the movement of mRNA to the cytoplasm of protein synthesis.

Allow the import of enzymes necessary for DNA transcription.

Ribosomes - cellular machinery involved in the synthesis of proteins.

structures of ribosomes are made in the nucleolus, then shipped out of the nucleus.

The large and small subunits both contain RNA and proteins.

can stay soluble in the cytoplasm as free ribosomes or attach to the endoplasmic
reticulum (bound ribosomes).

These two types of ribosomes produce proteins for different parts of the cell or for
secretion.

All protein are linear polymers of amino acids.

Condensation reactions polymerize amino acids, and Hydrolysis breaks these polymers
apart by adding water molecules.

There 20 different types of amino acids. All 20 amino acids have a common structure:

a central carbon atom bound to amino group

a carboxyl group

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 a hydrogen atom

variable side chain (”R”)

Polypeptide - a strand of amino acids covalently bound to one another through a

condensation reaction, which is catalyzed within the ribosome.
Process of Translation:

involves extruding an elongating chain of amino acids from the ribosome’s large
subunit.

The sequence of the amino acid polymer is determined by translating the information in
the mRNA - achieved by transfer RNA (tRNA).
tRNA matches the sequence of nucleotides on the mRNA, and carries the appropriate
amino acid chain to the next polypeptide chain.

Ribosome translation cause amino acids to polymerize into a primary structure called a
polypeptide. The C-N bond that results from this condensation reaction is called
Peptide Bond.

Variable side chains (R group) have distinct properties, they differ in size, shape, and
chemical properties.

some are hydrophobic, while others are hydrophilic.

hydrophobic side chains may aggregate in an aq environment.

hydrophilic side chains may be charge-polarized, capable to form ionic bonds.

some may form hydrogen bonds.

Free ribosomes translate proteins that will remain in the cytosol or be targeted to
organelles that include the nucleus, mitochondria, and chloroplast

include enzymes involved in glycolysis, or as the protein that makes up the

structural proteins of the cell.

other proteins can be transported through the nuclear pores into the nucleus to act
as histone proteins or transcription factors.

Unit 3: Protein Folding

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 💡 The three-dimensional folded shape of that polypeptide is essential to allow
for the proper function of the protein.

The amino acid side chain determine the 3D shape of proteins, which is crucial for their
cellular functions.

Globular proteins found in the cytosol have hydrophilic exteriors and hydrophobic
cores, allowing them to be soluble in the cytosol.

Proteins synthesized by bound ribosomes proceed through the endoplasmic

reticulum and acquire their folded, functional shapes in the aqueous environment of
the ER lumen.

A protein’s primary structure plays a significant role in determining its folding pattern.

After translation from mRNA to a protein, the polypeptide strand undergoes a folding
process influenced by the properties of the constituent amino acids.

Secondary Structure:

Alpha Helix
Covalent peptide bonds link the amino and carboxyl groups to form this chain.

Noncovalent hydrogen bonds cause the polymer to adopt a spiral or coil structure 🧬.
these H+ bonds occur between the carbonyl group of the carboxyl group in one
amino acid residue and the amide group of the amine group in another amino acid
residue located four positions away,

As a result, the variable side chains (R-groups) extend outward from the helix.
Emphasizing the significance of the difference among the 20 amino acids,
particularly their R-groups, in determining the overall properties of the protein
structure.

Beta Sheet

Aside from alpha helices, secondary structure can also include beta pleated sheets,
which is presented as broad lines with arrowhead in ribbon diagrams.

made up of parallel protein strands, with hydrogen bonds forming between the
carboxyl and amino groups of neighbouring strands.

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 Unlike alpha helices, beta pleated sheets have hydrogen bonds that create a
pleated or folded arrangement within this secondary protein structure.

The formation of a protein’s secondary structures is primarily driven by interactions

within protein’s backbone components.

The overall 3D shape or tertiary structure of a protein is determined by interactions

between the variable side chains or R-groups.

interactions, such as hydrogen bonds, van der waals interactions, covalent and
ionic bonds, and hydrophobic interactions. All of these collectively shape the
protein’s 3D structure.

There are also cellular mechanisms that assist protein folding.

Molecular Chaperones Chaperonins

bind to hydrophobic regions of the large molecular complexes that form

nascent polypeptide and prevent isolation chambers. Inside, a single
incorrect folding just long enough for nascent protein is isolated from other
the structure to form. proteins so that it can fold without
interference and no formation of
incorrect bonds.

Unit 4: Leaving the Endomembrane System and Reaching a Target

The enfolding of the cell membrane formed the endomembrane system, which includes:

nuclear envelope

endoplasmic reticulum

golgi apparatus

lysosmes

Aside from free ribosomes, there are ribosomes bound to the rough endoplasmic
reticulum. These ribosomes synthesize proteins that can enter the ER’s interior for
additional processing, which includes folding of the proteins.

mRNAs encoding proteins for the endomembrane system contarin a unique signal
sequence that when translated, it causes ribosomes to attach the ER.

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 Once formed, the signal sequence binds to a signal recognition particle (SRP),
which attaches to a signal recognition particle receptor (SRPR) on the ER
membrane.

This interaction enables the polypeptide to continue translation and enter the ER’s
central canal or lumen

Within the lumen, the signal sequence is removed, and the translated polypeptide
undergoes essential modification for its final processing and maturation.

While some proteins remain in the ER, many continue their way to their final
destinations within the cell by traveling in vesicles.

The ER is where proteins can undergo modification through Glycosylation (adding

one or more carbohydrate chains). This process contributes to protein stability,
proper folding, and cell-cell recognition.

Some glycosylation takes place in the golgi apparatus, which can include adding
carbohydrate groups.
Some proteins enter new vesicles and continue to the endomembrane system, where
they can be directed to various destinations.

The golgi serves as a central hub for these diverse protein-processing pathways.

Proteins leaving the golgi apparatus has a TAG (tagging molecule) that determines its
packaging into a particular type of transport vesicle.

This transport vesicle carry their own tags, guiding them to their designated
destinations.

When they reach their destinations, their phospholipid bilayers fuse with the target
membrane, such as the cell membrane, lysosome, or ER.

enables the release of soluble protein or the integration of transmembrane

proteins into the target membrane.

Tags and fusion plays crucial roles in directing proteins to their appropriate cellular
locations.

There are structural and motor components of the cell that are important in transporting
vesicles toward the cell membrane and back toward the nucleus.

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 Cytoskeleton - a dense network of fibers that helps maintain and alter cell shape.

Microtubules are protein polymers forming long fibers that traverse the cell, serving
as cellular roadways for vesicle transport

Motor proteins (i.e. kinesin and dynein) can attach to transport vesicles and move along
microtubules, powered by the energy released through ATP hydrolysis. Ensures efficient
vesicle transport within the cell.

Many soluble proteins are synthesized and folded in the cytosol where they continue to
function.
Others are transported to different places in the cell.

Proteins synthesized on free ribosomes - mitochondria, chloroplast, and perixomes

Unit 5: Protein Structure and Function Transmembrane Pores

Aquaporins are vital proteins found within the cell’s plasma membrane, facilitating the
movement of water across the membrane.

present in bacteria, animals, and plants.

has a hydrophilic core that permits the passage of water between the two sides of
the membrane.

consist of four protein subunits, forming a tetrameric aquaporin channel in their

quaternary structure.

Each subunit contains membrane-spanning alpha helices that create a central pore.

each monomer creates an independent water pore - allowing water movement in

both directions.

the central core accommodates several water molecules to pass simultaneously

through the channel.

do not change shape during water transport.

Prokaryotic cells have membrane pores

Proteins are crucial for various essential functions in our body, and their production is
encoded in our DNA.

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 must be accurately synthesized and directed to their intended destinations to
perform their roles.

Cystic fibrosis is a genetic disease characterized by the buildup of mucus in multiple

organs. This condition is associated with mutations affecting the function of the cystic
fibrosis transmembrane conductance regulator (CFTR) ion channel protein.
Consequently, one of the outcomes is the accumulation of dense mucus in the lungs,
which can lead to bacterial infections.

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