Proteins - Block 3

Question 1

What is the structure of a collagen molecule like?

Answer 1

It is a triple-stranded helical filament, with three helical α chains wrapping around each other.

Question 2

How does glycine influence the structure of collagen?

Answer 2

Gly residues exist in the core of the helical strand, facilitating the tight packing of the three strands.

Question 3

How can collagen be cross-linked to form fibrils and then fibres?

Answer 3

Lysine residues form intramolecular and intermolecular cross-links (Lys-Lys crosslinking). The resulting fibrils aggregate in the same way to form a fibre.

Question 4

What is the role of elastin?

Answer 4

Elastin endows tissues with elasticity.

Elastic fibres in the ECM provide resilience to recoil.

Question 5

How does elastin’s structure result in its mechanism of elasticity?

Answer 5

> It contains α-helical segments with Lys residues, as well as long hydrophobic regions,

> The K residues can cross-link to form a 2D network, facilitated by lysyl oxidase,

> When a force, the unstructured hydrophobic segments can extend, and they can recoil back to the original position thanks to the cross-linked α-helical segments.

Question 6

What is the role of fibronectin?

Answer 6

> It anchors cells and helps with cell migration <

a. It cross-links ECM molecule & links cells to the matrix, and b. it forms fibres

Question 7

What is the basal lamina?

Answer 7

> > A specialised ECM «

> Underlying epithelia

> Surrounds muscle cells

> Acts as a filter in the kidney

Question 8

What is the role of laminin?

Answer 8

> Important component of basal lamina

> Facilitates formation of 2D networks

> Interacts with other ECM proteins like type IV collagen “molecular sea” and perlecan

Question 9

What are 4 functions of sophisticated local cell-cell //EGM partnerships? (L.O.)

Answer 9

1. Imparting mechanical properties
2. Enabling cells to recognise & co-operate each other
3. Allow for the dynamic nature of tissues
4. Allow selective diffusion of molecules

Question 10

What two broad categories of subunit assemblies can a protein have?

Answer 10

1. Identical//similar subunits
   > Defined small number (haemoglobin)
   > Defined large number (a few viruses)
   > Variable number (MTs, actin, clathrin coats)
2. Several distinct subunits
   (nuclear pores, molecular machines)

Question 11

Meaning & examples of a (1) full-time complex?

Answer 11

> Function as stable oligomer
Several subunits
Icosahedral or helical symmetry

e.g. haemoglobin, polio virus

Question 12

Meaning & examples of a (2) part-time complex?

Answer 12

> Function as oligomer AND individual subunits

e.g. G-proteins, rhodopsin

Question 13

Meaning & examples of a (3) transient complex?

Answer 13

> Occur briefly in signal cascade
Rapid transmission of information

e.g. Ras and Raf (GTP binding to one complex causes affinity for the other to decrease & the complex breaks down).

Question 14

Meaning & examples of a (4) dynamic assembly?

Answer 14

> Rapid assembly//disassembly
AT//GTP-controlled

e.g. Actin (dynamic filaments) & tubulin (road network)

Question 15

Which motor protein carries cargo to the + end of the microtubule?

Answer 15

Kinesin

Question 16

Which motor protein carries cargo to the - end of the microtubule?

Answer 16

Dynesin

Question 17

What functions does an Actin filament have?

Answer 17

> Mechanical support
Cytoplasm traffic routes
Cell migration
Muscle contraction

Question 18

What functions does a MT have?

Answer 18

> Trafficking cargo

> Separating chromosomes

Question 19

What are three examples of molecular machines?

Answer 19

> Proteosome
GroEL//GroES
Nuclear Pore

Question 20

What is (MM1) the Proteosome?

Answer 20

> “Garbage-disposal machine”
Recognises + unfolds old proteins (caps)
Proteolytic sites cut chain up (inner chamber)

Question 21

What is (MM2) GroEL//GroES?

Answer 21

> A folding machine.
Chamber lets in polypeptide; ATP binds, causing GroES cap to bind & its polar inner surface helps prevent competing reactions, allowing protein to fold.
When protein is made, ATP is hydrolysed and GroES cap opens up.

Question 22

What is (MM3) the Nuclear Pore?

Answer 22

> Pore in the nucleus
Very complex structure
Made of 456 protein molecules

Question 23

What are the 4 components of communication & their roles? (L.O.)

Answer 23

1. Signal molecules = Messengers
2. Receptors = Signal Transducers
3. Intracellular Sig. Pathways = 2nd messengers
4. Target effector = Transcription regulator

Question 24

What are the 4 types in intercellular communication? (L.O.)

Answer 24

A. Contact-dependent

B. Paracrine (cell > cell signal molecules)

C. Synaptic

D. Endocrine (bloodstream)

Question 25

What FORM is the information in cell signalling?

Answer 25

Signal molecules

Question 26

How is the signal READ in cell signalling?

Answer 26

Receptor proteins

Question 27

How is the read signal COMMUNICATED in cell signalling?

Answer 27

Intracellular signal pathway (2nd messenger)

Question 28

What EFFECT does the communicated signal have in cell signalling?

Answer 28

Influences the effector protein (which controls transcription)

Question 29

What are the 3 classes of cell SURFACE receptors?

Answer 29

1. Ligand-gated channels 2. G-protein coupled receptors (GPCRs) 3. Enzyme-linked receptors

Question 30

What is the basic architecture of a GPCR? | *GOOD TO KNOW*

Answer 30

> 7 hydrophobic helical domains > Extracellular loops N-terminal loops (ligands bind here!) > Intracellular C-terminal loops (trimeric G-proteins associate here)

Question 31

What is the basic structure of a GPCR-associating G-Protein? | *GOOD TO KNOW*

Answer 31

> α, β and γ regions > α is a GTPase. > α can dissociate from β and γ subunits, which then form a heterodimer.

Question 32

Where is the GTP//GDP binding site on a GPCR-associating G-Protein?

Answer 32

α has the GTP//GDP binding site at its interface with the β//γ subunits.

Question 33

How is a GPCR-associating G-Protein anchored to the inside of the membrane?

Answer 33

With a fatty acyl PT-modification that's usually on the β//γ subunits.

Question 34

What regions of a GPCR-associating G-Protein are conformationally sensitive (cause a shape change)?

Answer 34

The "Switch Regions" on the α subunit that bind the outer PO4 of GTP.

Question 35

What is the effect of the α region of a G-protein dissociating?

Answer 35

> It binds to a GTP > The active conformation is activated > This interacts with effector proteins

Question 36

What does the β//γ heterodimer do when the α region of a G-protein dissociates?

Answer 36

It modulates other effector proteins.

Question 37

What causes the dissociated α region of a G-protein to re-associate?

Answer 37

> RGS proteins accelerate its hydrolysis of ATP | > It becomes inactive again

Question 38

What happens when dissociated α is inactivated (to complete the cycle)?

Answer 38

> It re-associates with β//γ > GDP is released > The G-protein re-associates with the GPCR

Question 39

What two factors influence the function of GPCRs? | *GOOD TO KNOW*

Answer 39

1. Ligand binding to the GPCR | 2. Influence of RGS proteins on the α active site

Question 40

What is the general action of a GPCR? | *GOOD TO KNOW*

Answer 40

1. α subunit binds to membrane effector 2. Effector activated; generates 2nd messengers 3. GTP hydrolysed to GDP & dissociates 4. α can now re-associate with β//γ

Question 41

What does the effects caused by different signals depend upon?

Answer 41

which signalling-pathway proteins are being expressed inside the cell.

Question 42

What are the characteristics of epithelial tissue? | *GOOD TO KNOW*

Answer 42

> Cells are tightly bound into sheets. > Not much ECM; thin layer (lamina). > cell-cell adhesions attach the cells & bear mechanical stress.

Question 43

What are the characteristics of connective tissue? | *GOOD TO KNOW*

Answer 43

> Cells are distributed sparsely. > Plentiful ECM. > Rich in fibrous polymers; matrix bears the mechanical stress.

Question 44

What are the three broad types of cell junction? | *GOOD TO KNOW*

Answer 44

1. Tight Junctions - Zip cells together, regulate molecular transport between cells. 2. Anchoring Junctions - Attach cells to each other and the ECM. 3. GAP Junctions - Mediate chemical//electrical signals.

Question 45

What does the ECM provide for cells?

Answer 45

A habitat in which they can build & maintain solid structures.

Question 46

List some important components of the ECM. | *IMPORTANT*

Answer 46

> Glycosaminoglycans (GAGs): massive hydrated polysaccharides that form a gel OR attach to core proteins to make proteoglycans. > Collagens: Principal ECM component, fibrous protein. > Elastin: Forms a network that stretches when mechanical force is applied and relaxes again. > Fibronectin: Links cells to ECM and each other (cross-linking). Has protein binding sites, some of which are cryptic and can only be revealed when the fibronectin fibrils are stretched. Interacts with actin; cells can migrate through the ECM along fibronectin fibrils. > Laminin: Forms 2D network in basal lamina. Also a ligand for integrin and has binding sites.

Question 47

In what way is the ECM dynamic?

Answer 47

There is significant two-way information exchange between ECM and cytoskeleton via integrins.