Chapter 3 Protein Structure & Regulation

Primary structure

The amino acids sequence of a polypeptide

Secondary structures

The conformations of segments of a polypeptide, but not the entire polypeptide

How segments are folded

Examples of secondary structure

The alpha helix

The beta sheets

Tertiary structure

The completely folded conformation of the entire polypeptide

Can be functional

Nonpolar side chains in a folded polypeptide

Tend to cluster at the core of the protein and away from the aqueous surroundings, leaving the polar and charged side chains at the surface.

Nonpolar amino acids form?

Transmembrane domains of membrane proteins

Polar and charged amino acids tend

To be at regions of proteins that are exposed to aqueous surroundings

Polypeptide maturation

Correct folding

Proteolytic cleavage

Chemical modifications

Formation of quaternary structures

Association of co-factors

Quaternary structure

Multiple polypeptides in a single protein

Hemoglobin consists

Two alpha globin polypeptides and two beta globin polypeptides

Each globin has?

An oxygen-carrying heme cofactor associated with it

Iron containing molecule (O2 binds)

A cofactor is?

A ligand that associates in the active site(s) and participates in the activities of the protein.

Defects in proteins example?

Sickle cell anemia

Collagen folding

Protein defect

Fibrillar collagens, the major structural proteins of connective tissues, are built of triple helices of procollagen polypeptides

Osteogenesis imperfecta

Brittle bone disease

TSEs

Fatal brain diseases characterized by spongy appearance

Prion hypothesis

Diseases are caused by incorrectly folded proteins

PrPc

Prion protein cellular

PrPsc

Prion protein scrapie

Stanley Prusiner

The propagation of infectious prions

Denaturants such as urea and heat can?

Unfold a polypeptide by breaking all non-covalent interactions between amino acids

Reducing agents such as 2-mercaptoethanol (2-ME) are necessary for?

Breaking disulfide bonds

Denaturants can not break

Disulfide bonds

Covalent bond that can form between adjacent side chains of proteins by an oxidation reaction

Can link two portions of the same polypeptide/different polypeptide chains

Elastin fibers

Rubberlike elastic meshworks present in the extracellular matrix of some tissues

Elastin fibers functions

They allow tissues such as skin, arteries and lungs to stretch and recoil without tearing

The cross links between single elastin molecules are?

Disulfide bonds

Phosphorylation

Covalent modification for activation and inactivation of many proteins

Protein kinases

Are enzyme that transfers phosphate groups from ATP to proteins

Three major protein kinases that can also phosphorylate

Serine

Threonine

Tyrosine

Histidine

Protein phosphatases

Enzymes that remove phosphate groups from phosphorylated proteins

Ligand is connecting to protein by?

Non-covalent bonds

cAMP is a ligand

That activates proteins

Not a cofactor

Inactive PKA is a tetramer:

Two catalytic subunits bound to two regulatory subunits

cAMP activates ___ by binding to the regulatory subunits, releasing the catalytic subunits

PKA

Enzymes accelerate chemical reactions in cells by converting

A substrate into a products

Enzymes have a specific

Substrate-binding site (active site)

Are enzymes altered in the catalytic process?

No

Enzymes can catalyze reactions in ____ directions

Both

Competitive inhibitors

Enzymes are recognized by them

Different from allosteric regulation

Allosteric regulation

A change in the conformation of a protein that affects its activity due to the binding of a regulatory molecule

Feedback inhibition

End product of a biosynthetic pathway inhibits the enzyme that catalyzes the first step of synthesis, causing the entire pathway to shut down

Negative allosteric regulation

Positive allosteric regulation

A hypothetical enzyme that catalyzes the oxidation of sugars in response to elevated adenosine diphosphate (ADP) levels

Ubiquitin

A small protein that is covalently attached to a target protein and is a label for regulation or destruction

Ubiquitylation is catalyzed by

Ubiquitin ligases

Types of ubiquilation

Mono

Multi

Poly (proteasomal degratation)

Ubiquitin ligase

Attaches several ubiquitins to the target protein

Cap domain of a proteasome (a protease complex)

Recognizes the polyubiquitylated target protein

Ubiquitins are?

removed and recycled

The proteasome degrades the target protein by?

Sequential ATP-dependent steps in the central cylinder

The central cylinder of the proteasome contains?

The active protease domain