BSR Ch.7 Post-Translational Regulation

What type of post-translational modification (PTM) is irreversible?

S-thiolation

Phosphorylation can occur at the side chains of what amino acids?

Histidine, Serine, Threonine, Tyrosine, Arginine, Lysine, Aspartate, and Cysteine

What enzymes phosphorylate their substrates?

Kinases

What enzyme dephosphorylate their substrates?

Phosphatases

What is the most abundant form of PTM phosphorylation?

Two-component system

What are the two amino acids in TCS?

Histidine and Aspartate

What is the second most common form of phosphorylation?

Ser/Thr kinases

What are the 3 different names for Ser/Thr kinases?

Hanks-type kinases, PASTA kinases, and Stk kinases

(T/F) Stk’s can phosphorylate TCS substrates at threonine residues.

True

What is it called when a Stk phosphorylates a substrate belonging to a TCS?

Cross-talk regulation

Unlike TCS kinases, Stk’s can have how many substrates?

Multiple

What 2 bacteria are examples of where Stk’s play a role in virulence?

S. aureus and Y. enterocolitica

What is the name of the Stk that gets secreted into host cells by Y. entercolitica?

YopO

What type of kinase system phosphorylates at tyrosine residues?

BY kinases

What residues get phosphorylated in Stk kinases?

Serine and threonine

What is the 4th type of phosphorylation system that phosphorylates at arginine residues?

Arg kinases

Why did Arg kinases previously go undiscovered for a long time?

Acidic phosphoproteosome sample prep

Arg kinases are found in what 2 bacteria?

S. aureus and B. subtilis

Arg kinases are believed to be involved in what type of processes?

Stress response, protein quality control, and spore germination

Glycosylation is the attachment of what?

Sugar (or glycan)

What are the 3 types of glycosyl linkages?

N-linked, O-linked, and S-linked

Where does N-linked glycosylation occur?

On the nitrogen of Asn or Arg

What enzyme attaches sugars to the nitrogen atom of Asn and Arg?

N-glycosyltransferases

Where does O-glycosylation occur?

On the hydroxyl group of Ser or Thr

What enzyme attaches sugars to the hydroxyl groups of Ser and Thr?

O-glycosyltransferases

Where does S-linked glycosylation occur?

At the thiol group of Cys

What type of glycosylation commonly occurs on cell surface proteins and on ribosomes?

N-linked

What type of glycosylation commonly occurs on flagellin, adhesin, and secreted toxins?

O-linked

What type of glycosylation commonly occurs on bacteriocins (antimicrobial polypeptides)?

S-linked

C. difficile causes what?

Colitis

How does C. difficile cause colitis?

Large clostridial toxins

What are the 2 large clostridial toxins?

TcdA and TcdB

How many domains does the large clostridial toxin (LCT) have?

4

What are the 4 domains of the LCTs?

A, B, C, and D

Which 3 domains are only involved in receptor mediated endocytosis and pore formation?

B, C, and D

What does the A subunit of the LCT (TcdAB) do?

Glycosylates the human Rho protein to inactivate it

What is the Rho protein in humans involved in?

Cytoskeleton organization

In ADP-ribosylation, where does the ADP-ribose moiety come from?

NAD

What enzyme covalently attaches the ADP-ribose moiety to the target protein?

ADP-ribosyltransferases (ART)

What enzyme removes ADP-ribose groups?

ADP-ribosyl hydrolases (ARH)

ADP-ribosylation of target proteins does what to their activity usually?

Inactivates

What is the example of the toxin that works by ADP-ribosylation?

Diptheria toxin

What does the diptheria toxin ADP-ribosylate?

EF-2

How does the diptheria toxin kill target cells?

Inhibit translation

What are the 3 components of the diptheria toxin?

A, T, and B

Which component of the diptheria toxin is the active toxin that ADP-ribosylates EF-2?

A

In the example of interbacterial competition, what secretion method was used by the “predator” bacterium that acts as a needle?

T6SS

In the example of interbacterial competition, what did the inserted ART ADP-ribosylate?

FtsZ

In the example of interbacterial competition, what determined whether a “prey” cell lived or died?

Presence/absence of proper cognate ARH

What are the 2 most common amino acid residues to get methylated?

Lysine and Arginine

What molecule usually serves as the methyl donor?

S-adenosylmethionine (SAM)

Where does Salmonella flagellin undergo methylation?

Lysine residue

What does methylation of Salmonella flagellin do?

Helps adhere to gut epithelial cells

In the example of Acinetobacter, what protein gets methylated at lysine residues that makes the bacteria “sticky”?

AtaA

What enzyme methylates AtaA in Acinetobacter?

KmtA

What residues are methylated in the ribosomal protein L11?

Lysine

DNA damage adaptive response involves methylation on what type of amino acid residue?

Cysteine

Chemotaxis involves methylation on what type of amino acid residues?

Glutamate

What was the primary example from lecture of a human prion disease?

Creutzfeldt-Jakob Disease (CJD)

Misfolding of what protein causes CJD?

PrP^c→PrP^sc

What were the other 2 examples of human prion diseases?

Fatal Familial Insomnia (FFI) and Kuru

What were the 3 animal prion diseases mentioned?

Chronic Wasting Disease (CWD), Mad Cow Disease, and Scrapie

What protein class helps monitor proteins to ensure they stay properly folded, especially in times of stress?

Chaperones

Why type of enzyme binds to hydrophobic patches on polypeptides and prevents aggregation?

Holders

What were the 2 examples of holders?

DnaK and DnaJ

What enzyme helps fold proteins and is ATP-dependent?

Folders

What were the 2 examples of folders?

GroEL and GroES

What are the 2 main types of proteins involved in protein degradation?

Hsp100/Clp and AAA+ proteases

What is the major component that has a barrel like structure with the interior lined with active sites capable of hydrolyzing peptide bonds?

ClpP