Cell Physiology UTA-Test 1

Proteins

Constitutes most of a cells dry mass, they are not only the cells building blocks, they also exucute the majority of the cells functions like growth and division, carrying oxygen and regulating chemical reactions

Action of proteins

Proteins in the plasma membrane form channels and pumps that control the passage of small molecules into and out of the cell. They also act as signal integrators that relay sets of information from the plasma membrane to the nucleus. Cell Physiology UTA

A protein molecule

Is made from a long unbranched chain of amino acids. Proteins are also known as polypeptides

Polypeptide backbone

Repeating sequence of atoms. Attached to these are the portions od a.a. that are not involved in peptide bonding but they give each a.a. its unique sequence #sidechains these side chains are what make each protein distinct

Twenty amino acids commonly found in proteins

Aspartic acid, glutamic acid, arginine, lysine, histidine, asparagine, glutamine, serine, threonine, tyrosine, alanine, glycine, valine, leucine, isoleucine, proline, phenylalanine, methionine, tryptophan, cysteine

Molecular Chaperones

Assist in protein folding. They bind to partly folded polypeptide chains and help them progress along the most energetically favourable folding pathway. Simply put chaperones simply make reaching the folded state more reliable

Protein Domain

A substructure produced by any contiguos part of a polypeptide chain that can fold independently of the rest of the protein into a stable structure

Ligand

Substance that is bound by the protein.

Ligand binding site

Consists of a cavity in the protein surface formed by a particular arrangement of amino acids

Cleavage of the polypeptide chain

Is an important step in the maturation of many proteins. A simple example is the removal of the initiator methionine from the amino terminus of many polypeptides

Signal sequence in membrane translocation

Signal sequence target the translocation of polypeptide chains across the plasma membrane of bacteria or into the ER

Proteolytic processing of insulin

The mature insulin molecule consists of two polypeptide chains joined by disulphide bonds. It is synthesized as a precursor polypeptide containing an amino acid terminal aignal sequence that is cleaved during transfer of the growing polypeptide chain to the ER

Ubiquitin-proteasome pathway

This is the major pathway of protein degredation in eukaryotic cells. Ubiquitin is used as a marker that targets cytosolic and nuclear proteins for rapid proteolysis

The UP pathway

Because this pathway is responsible for the degredation of several important regulatory proteins including those that control cell proliferation and cell survival and because cancer cells depend on the destruction of these proteins, the proteasome has emerged as a target for anti-cancer drugs

Two enzymes that catalyze protein folding

Protein disulfide isomerase and peptidyl prolyl isomerase

HSecretory pathway

Rough ER→Golgi→secretoey vesicles→cell exterior

Plasma mebrane proteins and lysosomal proteins also travel through the ER and the golgi before their final destination.

Also some proteins travel through this path but stay in the golgi or the ER.

Entrance of proteins into the ER

Represents a major branch point for the traffic of proteins within eukaryotic cells. Mamalian cells mostly go to the ER while they are being translated on membrane bound ribosomes. Those that are to remain in the cytosol are synthesized on free ribosomes and released into the cytosol when theie translation is complete

Proteins

Can be trabslocated to the ER either during synthesis on membrane bound ribosomes or fter their translation is complete on free ribosomes in the cytosol

Ribosomes engaged in the synthesis of proteins that are destined for secretion

Are then then targeted to the ER by a signal sequence at the amino terminus of the growing polypeptide chain

Cotranslational targeting of secretory proteins to the ER

1) as the signal sequence emerges from the ribosome it is recognized and bound by the signal recognition particle (srp)

2) the Srp escorts the coMplex to the ER membrane where it binds to the srp receptor

3)the srp is released, the ribosome binds to the translocon nd the signal sequence is inserted into the membrane channel.

4) translation resumes and the growing polypeptide chain is trabslocated across the membrane

5) cleavage of the signal sequence by signal peptidase releases the polypeptide into the lumen of the ER

Trnslocation of proteins

Translocation cn happen into the ER during their synthesis on membrane bound ribosomes or after their translation has been completed on free ribosomes in the cytosol.

Protein sorting

Proteins synthesized on free ribosome either remain in the cytosol or are transported to the nucleus, mitochondria, chloroplasts, or peroxisomes.

In contrast proteins synthesized on membrane bound ribosomes are translocated to the Er while their translation is in progress. They may either be retained in the ER, or transported to the golgi apparatus and then from there to lysosomes, the plasma membrane or the cell exterior via secretory vesicles.

Posttranslational translocation of proteins into the ER

proteins destined for postranslational import to the ER are synthesized on free ribosomes and maintained in an unfolded conformation by cytosolic chaperones.

their signal sequences are recognized by the Sec62/63 complex, which is associated with the translocon in the ER membrane. The Sec63 protein is also associated with a chaperone protein BiP, which acts as a molecule ratchet to drive protein translocation into the ER

Insertion of proteins into the ER Membrane

proteins destined for incorporation into the plasma membrane or the membranes of these compartments are initially inserted into the ER membrane instead of being released into the lumen. from the ER membrane , they proceed to their final destination along the same pathway as that of secretory proteins:

ER-Golgi-plasma membrane-lysosomes

Protein Folding

the ER is also the site of protein folding , assembly of multisubunit proteins, disulfide bond formation, the initial stages of glycosylation and the addition of glycolipid anchors to some plasma membrane proteins.

An important role of the ER

is to identify misfolded proteins, mark them and divert them to a degredation pathway

Iodine

necessary for production of thyroid hormones-deficiency =hyperthyroidism, dwarfism and mental retardation in kids, slow metabolism in adults

All biological systems are composed of the same 5 types of molecules

water, proteins, nucleic acids, carbohydrates, lipids

Functions of proteins

carry oxygen, cell growth and division , molecular motors, chemical reactions

Dogma of Biology

Gene- Protein- Function

Gene

a discrete unit of hereditary information located on the chromosomes and consisting of DNA

Genome

an organisms' genetic material

Genotype

the genetic makeup of an organism

Phenotype

the physical expressed traits of an organism

Hydrophobic a.a.

Tryptophan, tyrosine, methionine ans alanine.

Poorly interact with water, pack inside of the protein stucture to avpid awueous environment and likes to reside In lipid based plasma membrane

Hydrophobic a.a.

Tryptophan, tyrosine, methionine ans alanine.

Poorly interact with water, pack inside of the protein stucture to avpid awueous environment and likes to reside In lipid based plasma membrane

Hydrophobic a.a.

Tryptophan, tyrosine, methionine ans alanine.

Poorly interact with water, pack inside of the protein stucture to avpid awueous environment and likes to reside In lipid based plasma membrane

Hydrophobic a.a.

Tryptophan, tyrosine, methionine ans alanine.

Poorly interact with water, pack inside of the protein stucture to avpid awueous environment and likes to reside In lipid based plasma membrane

Carbon,hydrogen,oxygen and nitrogen

Make up the bulk of living matter and the molecules of life

Water,proteins,nucleic acids, carbohydrates and lipids

All biological systems are composed of the same 5 types of molecules

Function

Adding complexity to organic molecules adds function

ATP and GTP

Storage of energy

Proteins

Responsible for all cell function

Change of Glu to Val

This substitution creates a spot on the protein structure ,clumping leading to sickling of the red blood cells

Dogma of biology

Gene> protein> function

Translation

Process of converting information stored in genes into proteins and it only happens in the cytosol

Codons

Genetic information is written in? And they are triplet bases

Genes

Instruction manuals for proteins a.k.a cell function

Polymers

Formed by dehydration reactions

How cells make most of their large molecules

By joining smaller organic molecules into chains called polymers

mRNA

Copy of a gene

Protein making process

Dna-transcription- RNA -translation -protein

Peptide Bond

Dehydration sunthesis- condensation reaction between H3N group of one a.a and COOH group of a second a.a

DNA

Only information required for proper shape and function of the protein.

Only correctly folded protein can perform its function

DNA decides about a.a. sequence

Sequence decides how the polypeptide will fold

And where in the cell ot will reside.

And then the protein shape determines the function of that protein

Side Chainp

Unique to a.a.

Determines polarity and properties of a.a. and thus the structure of the protein.

Three main groups of a.a. based on chemical composition of side chains

Hydrophobic ,hydrophilic and special a.a

Three types of amino acids

Hydrophobic a.a.

Alanine, Valine,Isoleucine, leucine, Methionine, Phenylalanine, Tyrosine, Tryptophan

Poorly interact with water. Reside in lipid based plasma membrane

Hydrophillic a.a.

Lysine. Arginine. Histidine.(basic). Aspartate. Glutamate (acidic). Serine. Threonine. Asparagine and Glutamine (uncharged)

Special a.a.

Proline and Glycine. Create bending sites and contribute to 3d structure. Cysteines can form disulfide bonds

Amino acids properties

Decides about shape and in turn about interactions

Why no more than four shapes for protein

Peptide bonds are bery stuff and flat. Side chains also stick to the sides and form hydrogen bonds

Sickel cell anemia

Change in a.a. from Glu to Val

Transgenic

An organism that combines genes from two or more organisms

Translation

Codon directed addition of amino acids to polypeptide chain

Cytosol

Where sequencing of mRNA are translated into unique sequence a.a. in a polypeptide chain

Proteins

Have to be moved from their place of synthesis to their proper destination. They are all synthesized om a ribosome

Receptors

Plasma membrane

DNA polymerase

Nucleus

Catalase

Peroxisomes

Insulin

Outside

Cellular destinations

Cytosol. Nucleus. Membranes. Mitochondria. Chloroplasts. Peroxisomes. Lysosomes. Outside of the cell

How do proteins know where to go

The information about protein localization is encoded in the coding sequence except for those remaining in the cytosol

Targeting signal

Characteristic for the destination only. Can be cleaved by signal peptidasw or remain a part of protein. Can be located on N, C terminus or in the middle of protein

Gunter Blobel

Received nobel orize in physiology and medicine for discovering transport signals

What is needed to sort proteins into their destinations

Targeting sequence. Specific receptor on the destination organelle. Translocation channel. Energy and sometimes chaperones

Nuclearly encoded proteins have five major destinations

Cytosol. Nucleus. Peroxisomes. Mitochondria and ER

Proteins are synthesized in two divergent mechanisms

On free cytosolic ribosomes. On ribosomes attatched to rough ER(these are secreted)

Translation of cytosolic proteins

Synthesized on free cytosolic ribosomes. If there is no targeting sequence then it qill finish here and dropped into the cytosol

Translation sorting of proteins destined to nucleus, mito or peroxisomes

Synthesized on cytosolic ribosomes. Then based on destination from coding sequence it is released to the cytosol and sorted later

ER is just an extra step to their destination

Every other protein has to stop in the ER first.

Ribosomes

Decoding and synthesis takes place in the cavity between subunits

ER pathway of protein synthesis

In secretory pathway translocation occurs simultaneously with translation #cotranslationally.

ER TARGETING SEQUENCE

Initial steps in synthesis pf Secretory proteins

Translation starts. Then continues until signal sequence emerges from ribosomal tunnels. A signal recognition (srp) binds to signal sequence. SRP directs the complex to the er membrane. SRP binds to srp receptor on er membrane . RIBOSOME docks to a translocon. Srp dissociates. Translation continues while peptide is translocated into ER. Once in ER signal peptidebis cleaved by signal peptidase

Insertion of integral membrane proteins into ER membrane

To be inserted into the cell membrane proteins they have to be first inserted into the ER MEMBRANE. and it is guided by special sequences. And they must be oriented properly

Synthesis of insulin receptor

Single transmembrane domain. C-terminus inside the cell. Signal sequence guides it to ER. AND then stop transfer sequence to stop translocation and insert it into the membrane

Ion channels. Receptors or transporters

Have multiple passes through the membrane

Insulin

N terminal targeting sequence only

Posttrabslational modification

Folding(disulfide bond formation). Glycosylation(addition of carbs) and proteolytic cleavage. Only proper modified proteins are transported from ER to final destination

Molecular chaperones

Folding of proteins is aided by this

Chaperones that facilitate folding

Lectins. BiP and peptidylprolyl isomerases

Ubiquitin-proteasome pathway

Misfolded or unfolded proteins are transported back to the cytosol and degraded in this pathway

Asparagine

Sugars are always added to this end in N linked Glycosylation

ABO blood types

These are determined by O linked oligosaccharides

Processes heavily relying on glycosylation

Immunity. Cancer. Fertization and implantation. Cell adhesion a.k.a wound healing. Arthritis

Fucose, galactose, glucose, Mannose, N-acetyl galactosamine, N- glucosamine, N acetyl neuraminic acid , xylose

Eight sugars in human glycoproteins that are critical to vital processes

Muscular dystrophies due to glycosylation defects

Walker-warburg syndrome

Muscle eye brain disease.

Fukuyama muscular dystrophy

Protein processing in Golgi

Properly folded and modified protei s will move to golgi.

Nore post translational modification-further N linked and O linked and proteolytic cleavage

Targeting to lysosomes

Is done by post translational glycosylation. Protein destined to lysosomes will have mannose-6-phosphate attached in the ER

Delivery of lysosomal enzymes to lysosomes

M-6p binds to ER membrane receptor. Polymerization of clathrin and vesicle formation. Sorting to endosomes and proteins detach from receptor and become lysosomal enzymes