PSIO 404 Objectives for Exam 1

Question 1

Define signal transduction

Answer 1

established term for molecular mechanism by which a cell processes exogenous and endogenous info.
AKA as cellular data processing

Question 2

Describe the goal of signal transduction

Answer 2

finding the response that optimally safeguards survival
-existing living systems are successful living systems, having experiences a long historical refinement of their processing capabilities in this regard

Question 3

Discuss some general composition of a system that performs signal transduction

Answer 3

the composition is a data processing protein network which acts as a switching device capable of logical decisions

Question 4

List some characteristics of living systems as exhibited by cells

Answer 4

-survival factors
-death factors
-a ti-growth factors
-ECM
-hormones
*to find the response that optimally safeguards survival

Question 5

Discuss why a cellular data processing network is inseparably linked to cell architecture and mobility

Answer 5

1. input arrives primary at the plasma membrane and processing proceeds inward
2. integration of information to make decisions involves things localization and results in long term changes in the gene expression (histones)
3. cell response can involve cell movement or changes in cell shape both involving cytoskeletal proteins
   EX: ligans to the receptor into the cell for a cellular response into the nucleus for a change in gene expression

Question 6

Discuss why a cellular data processing network is inseparably linked to metabolism

Answer 6

1. signal processing creates order out of disorder which is work and work requires energy
2. without exception, life at all scales required both successful data processing and successful energy metabolism and the linkage should be expected

Question 7

Discuss information flow veteran cells (why is is done, transmitters verse receivers, signals, encoding versed decoding, and the importance of meaning)

Answer 7

a message is received in a transmitter and then is encoded and sent in the medium where the signal is decoded and sent to the receiver to gain the meaning and release a response

Question 8

Discuss input signals for signal processing proteins and explain the concepts of allosteric interactions (allostery) and cooperatively

Answer 8

-allostery describes regulatory domains as where input signals act to shift allosteric equilibrium towards off or toward on
-the non-covalent binding of a signal molecule to alter the conformational equilibrium for a signal-processing protein

Question 9

Define “noise” and explain how data processing protein networks filter it out

Answer 9

-noise is irregular signal intensities and the cell can noise filter by assembling its signaling proteins into oligomeric complex which is a quaternary structure. this is because oligomeric complexes take advantage of not only allostery but also cooperativity between signaling proteins
EX: positive cooperativity of cAMP binding in protein kinase A (PKA) because it binds 3 cAMP molecules to promote the binding of the 4th cAMP but no output is generated until the 4th one binds

Question 10

Describe protein isoforms and explain why are they important in cell signal transduction

Answer 10

protein isoforms are different versions of the protein and they are important because they may function differently and may be restricted to expression in particular cell types. In cell signal transduction you want different isoforms to allow specific tissue to have a specific function
EX: there are 4 PKA isoforms for the catalytic subunit expressed in different tissues

Question 11

Explain the concepts of redundancy and how is it achieved

Answer 11

redundancy if for a cell to produce multiple isoforms of a given signaling protein and this can be done by
1. expressing different genes
2. using alternate gene promoters
3. post transcriptionally modify a transcript (alternative splicing)

Question 12

Describe why redundancy is critically important for signal processing by cells

Answer 12

This is important because if one of the spices is messed up or does not get the job done then you have other options and ways to get the job done

Question 13

Differentiate between “public” and “private” intermolecular signaling in cells

Answer 13

private = signaling interaction between proteins, short range, can be with interaction domains or phosphorylation
public = signaling interaction with 2nd messenger such as cAMP, long range

Question 14

Explain the importance of transitoriness in cell signal transduction

Answer 14

so that a signal can be turned on but so that it does not stay on and avoid overstrain the cell used transitoriness, or inactivation mechanisms so that the signal is not indefinite

Question 15

Describe the modular design of signal transduction in proteins

Answer 15

once a bond, cAMP for non covalent, binds to the protein and activate it then it can be enzymatically cleaved and the protein can become inactive

Question 16

Compare and contrast terms hetertypical and homotypical when it comes to interaction between “domains” in proteins

Answer 16

homotypical - interact with their own type of domain (oval oval )
hetertypical - interact with different type of domain (oval tirangle)

Question 17

List the interaction domains and interaction partners shown in table 1.2

Answer 17

Group 1: the recognition site is a short amino acid sequence
Group 2: the recognition site is a short amino acid sequence containing a covalent modification
Group 3: the recognition site is a membrane component
Group 4: the interaction domain is identical with the recognition domain (homotypical interaction)

Question 18

Discuss how posttranslational modifications create interaction partners for group 2 interaction domains in proteins

Answer 18

this group is unique because they attach to modified amino acid sequences requires phosphorylation in order to work

Question 19

Explain how cellular swiping elements (data processing proteins) can be switched ON or OFF by signals

Answer 19

requires conformational changes to permit or prevent interaction
1. enzymatic removal
2. competition
3. allosteric interaction

Question 20

Describe the function of adapter and scaffold proteins

Answer 20

adapter protein govern association of one protein with another
scaffold proteins vastly speed up signal transduction by pre assembling signaling proteins on a scaffold

Question 21

Explain why data processing, the goal of which to minimize uncertainty, is coupled with chemical reactions delivering a large amount of energy

Answer 21

because there is no order and certainty without work and word requires energy
with no energy leads to degradation and disorder
-minimizing uncertainty is creating order out of disorder with requires coupled processes that provide energy, and these we call swithcing processes

Question 22

List the sources of energy which drive cellular data processing

Answer 22

oxidation, nitrosylation
GTP hydrolysis
ATP hydrolysis
phosphorylation
ubiquitylation
acetylation
poly (ADP-ribosylation)
proteolysis
discharge of membrane potential

Question 23

List the most frequent switching reactions of cellular signal processing and organize them by covalent vs non covalent and by ATP dependent vs ATP independent

Answer 23

oxidation = covalent, ATP -independent
nitrosylation = covalent, ATP -independent
GTP hydrolysis = non - covalent, ATP -dependent
ATP hydrolysis = non-covalent, ATP -dependent
phosphorylation = covalent, ATP -dependent
ubiquitination = covalent, ATP -dependent
acetylation = covalent, ATP -dependent
poly (ADP-ribosylation) = covalent, ATP -dependent
proteolysis = covalent, ATP -dependent
discharge of membrane potential= non -covalent, ATP -dependent

Question 24

Discuss two purposes for covalent modifications of signal proteins

Answer 24

1. persistent conformational change because the protein can now act on substrate
2. generation of a contact site so the protein can now interact with a different protein that contains a group 2 domain

Question 25

De able to define a redox reaction

Answer 25

A chemical reaction that takes place between an oxidizing substance and a reducing substance

Question 26

How can one determine if a protein is “sensitive” to the redox reaction

Question 27

Describe the general design of a redox switch, including the roles of enzymes and reactive oxygen species (ROS)

Answer 27

the oxidation switch is driven by the concentration of ROS, the synthesis of redox enzymes used for aerobic respiration there must be a surface sulfhydryl group provided by the amino acid cysteine because they are the first amino acids in a cell to be modified when ROS goes up and the reductase glutathione and thioredoxin turn off the switch

Question 28

Be able to explain the origin of the driving energy for a redox switch

Answer 28

input signal oxidase, H2O2 or O2

Question 29

List three types of proteins modified by the redox switch

Answer 29

transcription factors, protein kinases, and phosphates

Question 30

Discuss the three ROS we covered, their relative toxicity, and their relative involvement in signaling

Answer 30

H2O2,
O2 which is a superoxide anion radical
and Oh which is never used because it is extremely dangerous

Question 31

Describe oxidative stress and its consequences

Answer 31

protein oxidation, lipid and fatty acid oxidation, mtDNA, nDNA damage and aging and diseases of again, inflammastion, alcohol, hypoxia

Question 32

Briefly describe nitrosylation and define nitrosative stress

Answer 32

activated by the presences of nitric oxide that is produce by the enzymatic oxidation of arginine and it target surface accessible -SH groups from the amino acid cysteine to regulate the expression of over 100 proteins but can lead to nitrosative stress which is the pathological overproduction of NO. it can be turned off by denitrosylation using glutathione or thioredoxin

Question 33

Briefly describe the importance of G-proteins

Answer 33

g-proteins hydrolyze GTP and they are important because they yield the same amount of energy as ATP hydrolysis and are in almost every kind of signaling cascade in eukaryotes
-the rate of hydrolysis of GTP and the exchange of GDP for GTP are both controlled by inputs
-turned one by GDP-GTP exchange

Question 34

Name and describe the two superfamilies of G-proteins including a brief desorption of the p21 Ras protein

Answer 34

-small G -proteins (p21 Ras protein)
-p21 Ras protein functions in cell differentiation, proliferation, cytoskeletal organization, nuclear transport
-small g protein activity of modulated by GEF and GAP
-large G -protein (transducin)
-large g protein activity of modulated by GEF and GAP

Question 35

Describe how G -protein amplify signals, self inactive and act as organizers

Answer 35

to amplify signals the activation of adenylate cyclase form large amounts of cAMP in response when it is activated by a G -protein
-This means a signal-processing protein is able to increase the strength of a signal as it performs its actions.
-they are self rectifying (inactiving) because GTP hydrolysis allows a G protein
-This means a signal-processing protein is able to self-inactivate as it performs its actions
-G proteins mediate assembly of signaling complexes as organizers
-This means a signal-processing protein is able to assemble signaling complexes as it performs its actions.

Question 36

Discuss how the energy of GTP hydrolysis is used by G proteins

Answer 36

GTP hydrolysis increases order in g protein structure

Question 37

Describe the catalytic effect of GEF’s

Answer 37

G - GTP (on state) has low energy and lower order
G GDP (off state) has high energy and high order
-with GEF it lowers the activation energy (works like a catalyst)

Question 38

Describe the importance of GAPs for small G-proteins and the influence of RGSs on large G proteins

Answer 38

GAPs provide the required arg residue for small G -protein
RGS influence GTPase domains for large G proteins because the domains already have arg residue on them

Question 39

Group 1 table 1.2

Answer 39

-pro-x-x-pro = SH3
-arg-x-x-lys = SH3
-pro-pro-x-tyr = WW
-x-y-z-VAL-COOH 0r -leu-COOH = PDZ

Question 40

Group 2 table 1.2

Answer 40

-phospho-Tyr = SH2, PTB
-phospho -Ser = 14-3,WW,MH2
-phospho - Thr = FHA,WD 40
-acetyl-Lys - bromo
-methyl-Lys = chromo
-ubiquityl-Ly, polyubiquitin -Lys = UIM, UBA, CUE, UEV, PAZ, NZF

Question 41

Group 3 table 1.2

Answer 41

-diacylglycerol = C1
-phosphatidylserine = C2
-phosphatidic acid = C2
-phosphoinositides, Gby subunits = PH
-3-phosphorylated phosphoinsoited = FYVE, PX

Question 42

Group 4 table 1.2

Answer 42

death domain (DD) = DD
death effector domain (DED) = DED
Card = card
PDZ = PDZ
sam = Sam

Question 43

Name the two families of ATP hydrolysis switches, and describe why these
ATPases are genuine switches.

Answer 43

1. Chaperone proteins use ATP hydrolysis to regulate conformational charges in target proteins (client proteins)
2. AAA+ Proteins use ATP hydrolysis switch to regulate association and dissociation of signal transducing protein complex
   -used to create order

Question 44

Discuss the function of molecular chaperones and give an example.

Answer 44

-they are promoted by scaffold proteins which promote ATP hydrolysis like GAPs promote GTP hydrolysis for G-protiens and are catalyzed by NEFs to produce client proteins
-chaperones use ATP to generate order in themselves and transfer it to their client proteins to result in re folding of the client proteins into the functional state
EX: HSP70 and HSP90 (heat shock proteins) to stabilize functional state of steroid hormone receptor in cytoplasm using ATP

Question 45

Describe the ATP hydrolysis switch as performed by chaperones: inputs, output, and general mechanism of switching

Answer 45

molecular chaperones enable signal-processing client proteins to be converted from their native state (more thermo stable and lower free energy) back to their functional state (properly folded, higher energy state, less stable)

Question 46

Describe the ATP hydrolysis switch as performed by AAA+ proteins: inputs, output, and general mechanism of switching.

Answer 46

inputs = nucleotide exchange factors (NEF) which are proteins which speed up ADP-ATP nucleotide exchange for AAA+ proteins and ATPase catalyze and promote scaffold proteins a protein

Question 47

Discuss the function of AAA+ proteins and give an example.

Answer 47

ATPase Associated proteins with various cellular Activities
-act as unfoldase to dissociate protein protein and protein - nucleic acid complexes
EX: the formation of initiation complex DNA replication is regulated by 10 different AAA proteins
*some AAA proteins are proteases with an additional protease catalytic domain in their structure to terminate or promote signaling by eliminating stimulatory or inhibitory signaling proteins

Question 48

Describe the phosphorylation switch: inputs, output, and general mechanism of switching

Answer 48

-the major switching reaction of cellular data processing
-OFF to ON is catalyzed by protein kinase
ON to OFF is catalyzed by protein phosphatase
-three phosphate donora are ATP, GTP, PEP

Question 49

Briefly explain the biochemistry of reversible protein phosphorylation, which
amino acids can be phosphorylated, and the type of enzymes involved

Answer 49

-only specific amino acids Tyr, Thr and Ser

Question 50

Name the two major (super-)families of protein kinases.

Answer 50

Histidine Autokinase Family and Eukaryotic Protein Kinase Family

Question 51

Describe the eukaryotic protein kinases: their general structure and mechanisms of activation, including three mechanisms of inhibition used and the two (or
three) steps required to achieve full activation

Answer 51

:
1. conformational change
2. stabilization of chaperone protein
3. activation of loop phosphorylation
activation :
1. removal of inhibitory sequence from the oral groove of enzyme
2. chaperone protein is often required to maintain the active yet unstable enzyme conformation
3. the activation look is phosphorylated to fully activate the kinase

Question 52

Discuss the three major effects of phosphorylation on proteins.

Question 53

Name and very briefly describe four major families of Ser/Thr kinases

Question 54

Name and very briefly describe five major families of phosphatases. Include a short discussion of the regulation of Ser/Thr phosphatases vs. Tyr phosphatases.

Question 55

Define phosphorylation cascades or phosphorelays, list their major functions, and describe the design and function of MAP kinase cascades.

Question 56

Explain the role of the PTP phosphatase in the cellular pathophysiology of Bubonic Plague

Question 57

For the ATP-Hydrolysis Switch, the energy from ATP hydrolysis is immediately used to

Answer 57

generate order in the chaperone protein’s structure.