BGM1002- L4: non globular proteins

what is a protein oligomer

protein chains come together in a particular quaternary structure

homo- same sequences or hetero- different sequences

What are globular proteins?

Well folded, distinct secondary and tertiary structure, they are mainly enzymes.

What a protein fibres?

Globular proteins that assemble into fibrous quaternary arrangements.

What are examples of protein fibres?

Cytoskeletal proteins, flagella, pilli, filamentous viruses.

What are the characteristics of protein fibres?

Strong, dynamic and can interact with other proteins/DNA.

What is the cytoskeleton?

A network of protein filaments that links the membrane to nucleus in eukaryotic cells.

What is the function of the cytoskeleton?

Provides mechanical stability, used to transport things as as diffusion distance is too large in eukaryotic cells, provides a template for cell wall construction and responds to changes in the environment.

What are the key classes of the cytoskeleton?

Microfilaments, intermediate filaments, microtubules.

What are microfilaments?

Primarily made up of actin, located underneath the plasma membrane. Actin binds and hydrolyses ATP, they regulate the shape and movement of the cell surface membrane.

how is dynamic behavior of actin filaments created

ATP-actin has a high affinity for other molecules and ADP-actin has a low affinity. actin is added at + ends and dissociates at - ends. ADP is exchanged for ATP in free actin which generates forces to be used in cell motility

What are intermediate filaments?

Formed from alpha helices that wrap around each other, this makes them very strong. They are mainly found in the cytoplasm, they provide cell adhesion, cellular organisation and form muscle fibres.

What is keratin?

• an intermediate filament

• Coiled structure to stabilise hydrophobic interactions, produces filaments.

• Alpha makes up hair, nails, claws, feathers, skin.

• Beta keratin makes up scales, nails of reptiles and tortoise shells.

What is vimentin?

• Coiled to form a filament to form a fibrous structure of 8 tetramers, it anchors organelles in the cytoskeleton.

• It is attached to the nucleus, ER and mitochondria.

what is alpha-internexin/nestin

• proteins that are key elements of neurofilaments

• key structural elements of axons

• coiled coils

What is lamin?

A coiled structure, provides structure and regulation in the nucleus. It interacts with the nuclear membrane, it is very sensitive to stretch and feedbacks to cell on mechanical stress. has a coiled coil domain and a terminal head

What are microtubules?

• A key component of the cytoskeleton, made up of alpha and beta tubulin. They are nucleated at organising centres.

• They elongate at both ends but it is more rapid at the positive end, they are highly dynamic.

• bind and hydrolyze GTP

Why are microtubules associated with proteins important?

They allow exo/endocytosis, regulate microtubule stability, interact with other parts of the cytoskeleton and traffic vesicles in the cell. (eg dynein and kinesin)

How are muscle cells with myofibrils arranged?

In a repeating sarcomere structure consisting of: actin, myosin, troponin, tropomyosin, titin

What is the importance of titin?

It prevents the over extension of muscles.

What are cilia?

Cell extensions in eukaryotes, they have a complex microtubule arrangement. - - They play a key role in motility, in epithelial cells they move mucus and there are sensory cilia in hair cells.

What are flagella?

• They play a key role in motility, very similar to cilia but vary in length and dynamics

• in bacteria/archaea-protein based helical filaments with motors connecting to cell membrane (motor is ATPase)

• motor can spin anti/clockwise in response to sensing environmental signals

what is pilli

• protein filaments on the surface of bacteria and archaea

• conjugative appendage

• has a globular domain with long alpha helix extension

• transfer ssDNA through pilus into host cell a key mechanism in antibiotic resistance

what is fimbriae

• surface attachment through adhesion domains on ends

• 10 nm -2 µm long

• cells can have many

• key for virulence of pathogenic bacteria

collagen

• triple helix structure- 3 alpha helices- 2 identical a1 chains and a third a2 chain with a different sequence

• cross linked through surface lysines through condensationsilk

silk

• fibrous protein made by several insects

• silkworm silk- made of fibroin and sericin proteins. fibroin has heavy and light variants with disulphide links between the chains. formed of beta sheets. sericin is beta sheet rich and is H bonded to fibroin

• spider silk- different types with different physical and mechanical properties, has repetitive glycine and alanine rich blocks

what are intrinsically disordered proteins

• no regular tertiary structure

• can be whole proteins or just domains of a bigger protein

• still stable and active

• can undergo transition to ordered/ disordered in response to environmental or cell signals

What is the problem with protein misfolding?

• almost all proteins can be miss folded to form predominantly beta sheet structures

• Proteins that aren't folded correctly start to stick together, they are very difficult to break down. accumulation is key in many diseases e.g. Alzheimers, Parkinson's etc.

what is amyloid

• a protein that can damage cells

• distinct cross beta sheet arrangement

• structural variations seen across kingdoms and in different diseases