Biochem Chapter 22 Protein Synthesis and Turnover

_______ is the process by which the information encoded in an mRNA is translated into the primary structure of a protein

Translation

3 main RNA component for mRNA to protein

rRNA ribosomal

mRNA messenger

tRNA transfer

A series of three nucleotides in the mRNA, known as a ______, is required to specify each amino acid.

codon

Three of these codons are stop codons, used to signal the termination of protein synthesis; they do not specify an amino acid.

UAA, UAG, UGA

UGA AG AA

The remaining 61 codons specify the 20 amino acids, which illustrates that the genetic code is _______, meaning that more than one codon can specify a specific amino acid.

degenerate

What is the start codon

AUG

Synonymous vs Nonsynonymous Mutation

Synoymous do not change protein sequence (silent)

Nonsynonymous can cause missense or nonsense (premature termination)

_______ are the molecular machines that conduct protein synthesis.

Ribosomes

Tetracycline is a broad-spectrum antibiotic that inhibits the protein synthetic machinery of the bacterial cell by binding to the ___ site of the ribosome.

A

Tetracycline need to be taken for entire perioid or bacteria may grow again and lead to resurgence of infection

To preserve the unambiguous codon–amino acid correspondence dictated by the genetic code, the individual aminoacyl-tRNA _______ are capable of identifying the small differences between each unique tRNA in order to pair the correct tRNA with its cognate amino acid.

synthetases

It proofread and can also remove wrong attachment

The wobble hypothesis states that the ____ end of the codon is the least stable and most flexible

3’

G can grab C and U

I can grab A or C or U

Shin-Dalgarno Sequence

Sequence in prokaryotic mRNA that direct ribosome to beginning of protein-coding region

Prokaryotic mRNA lack cap to faciliate ribosome binding

Using the energy of ATP _______, the complex scans the mRNA to locate the first AUG codon.

hydrolysis

Is methionine the first amino acid in bacterial proteins

No fmet is but it is also encoded by AUG just read differently

What is eiF2B

Binds GTP to Met-tRNA to initiate translation

Mutation causes slowed or stalled translation and cells fail to make protein

Termination of protein synthesis in both eukaryotic and bacterial cells is accomplished when the ____ site of the ribosome reaches one of the stop codons of the mRNA.

A

Proteins called _______ _______ _______ recognize these stop codons and cause the protein that is attached to the last tRNA molecule in the P site to be released

eukaryotic releasing factors

Peptidyl ______ is the activity responsible for peptide bond formation during protein synthesis.

transferase

_____ _____, the result of errors in protein folding, develops in many chronic conditions, including obesity, diabetes, and cancer

ER Stress

Proteins require the help of a class of proteins called ________ to achieve their correct native structures.

chaperones

Promote correct folding, assembly, and organization of proteins

______ ______ ______(HSP) are a group of chaperone proteins that are expressed by cells in response to high temperature.

Heat Shock Protein

Assist in refolding of denatured protein not only as result of heat

The protein GRP78/BiP binds unfolded protein and traps it in ER preventing further transport and secretion. The unfolded protein is then routed to the _____ _____ _____ (ERAD) pathway, which facilitates export to the cytosol and proteasomal degradation of the misfolded protein

ER associated degradation

A condition known as ER stress develops if _______ and _______ activities are overwhelmed, leading to the accumulation of protein aggregates in the lumen of the ER.

chaperone, ERAD

ER stress activates the ______ ______ _______ (UPR) in a GRP78/BiP-dependent manner, which increases the expression of several chaperones and ERAD proteins.

unfolded protein response

What does phosphorylation of eIF-2 does

Initiation of translation slow down or stops

If ER stress is too severe, _______ will be triggered to eliminate the cell.

apoptosis

ER stress and the UPR also inhibit _______ signaling, causing insulin resistance, and play a role in the development of pathology in obesity and type 2 diabetes mellitus

insulin

A signal peptide is a short stretch of 20-30 amino acids located at ______ terminal that determines where the protein will go in the cell.

The signal sequence is recognized by ______

amino N

SRP (Signal recognition particle)

SRP stop translation and protein proceed to ER to Golgi for final destination

Protein without signal sequence stay in cytoplasm

Mitochondrial vs Nuclear Proteins

Mitochondrial are transported after translation, must be unfolded before transport

Nuclear contain NLS and do not require unfolding

The endoplasmic reticulum and Golgi apparatus are major sites of _______ modification of proteins.

posttranslational

n the ER, an enzyme called ______ ______ removes the signal sequence from the amino-terminus of certain proteins, resulting in a mature protein that is 20–30 amino acids shorter than that encoded by the mRNA.

signal peptidase

Unlike ______, damaged proteins are not repaired but degraded

DNA

For certain proteins, an internal PEST (ProGluSerThr) sequence signals their rapid _______, and proteins with N-terminal arginine generally have short half-lives compared with proteins with N-terminal methionine.

degradation

________ ingest and degrade damaged mitochondria and other membranous organelles.

However, most soluble cytoplasmic proteins are degraded in structures called _______

Lysosomes: Degrade organelles and membrane structures

Proteasomes: Degrade soluble proteins

Proteins destined for proteasomal destruction are covalently tagged with a chain of a highly conserved 76–amino acid protein called ______, which is found in all cells.

ubiquitin

E1

E2

E3

Ubiquitin activating enzymes (binds and activate ubiquitin)

Ubiquitin carrier protein (Carries activated ubiquitin)

Ubiquitin protein ligase (Transfers ubiquitin to substrate)

Multiple myeloma (MM) is a cancer of ______ cells (B lymphocytes), which are normally found in bone and synthesize antibodies as part of the immune system

plasma

One successful treatment option for patients with recurring MM is _______, an inhibitor of protease activity in the proteasome.

bortezomib