BIOL 3000 Proteins

Proteins

Large biological molecules (macromolecules) consisting of one or more polypeptide chains that perform a wide variety of functions in living organisms.

Structure gives rise to?

Function

Functional diversity and versatility of a protein derives from

-Chemical diversity of the constituent amino acid side chains

-Flexibility of the polypeptide chain

-Large number of ways in which polypeptide chains interact with different amino acids and fold

Overview of protein function

Binding, catalysis, switching, structural

Chemical diversity of the constituent amino acid side chains

There are 20 unique amino acid side chains

They each have different tendencies to interact with one another and other molecules

Non-polar (hydrophobic)

The tendency to repel water and pack closely against each other

They are on the inside

Non-polar examples

Alanine, valine, leucine, isoleucine, proline, methionine, phenylalanine, tryptophan

Polar (hydrophilic)

The tendency to form hydrogen bonds with one another, to the peptide backbone, to other molecules and to water

Polar examples

Glycine, serine, threonine, cysteine, tyrosine, asparagine, glutamine

Charged

The tendency to reside on the outside of a globular protein and interact with the other side chains or macromolecules to give structure.

There are repulsion and attraction forces that alter the structure of the protein

The functional structure of protein folds onto each other

Positively charged (+) examples

Lysine, arginine, histidine

Negatively charged (-) examples

Aspartic acid, glutamic acid

Non-covalent bonds

Hydrogen bond, ionic bond, hydrophobic interactions

Covalent bonds

Disulfide bond between amino acids

Backbone of all amino acids

An amino group at the front, an alpha carbon and side chains, and a carboxylic group at the back

Where do interactions occur?

At the side chains (R-group)

Peptide bond

A covalent bond between the carboxyl carbon and the amide nitrogen of two adjacent amino acid residues

Forms water

Polypeptide chain

Globular 3-dimensional protein

Flexibility of the polypeptide chain

The carboxyl carbon, carboxyl oxygen, and the amide nitrogen of the next amino acid are on a peptide plane which is coplanar

N-alpha carbon and the alpha carbon-carbon bonds are single bonds allowing free rotation provided there is no interference from the side chains

Covalent bonds

The sharing of electron pairs creating a very stable interaction

Stronger interactions

Ex: amide bonds of the amino acid backbone, disulfide bonds in some excreted or exterior surface proteins between the side chains of cysteine residues

Electrostatic bonds

The interaction of amino acids based on their charge

Weaker interactions

Ex: hydrogen bonds which occur when hydrogen has a significant positive charge and attracts significantly negatively charged atoms; Van der Walls Interactions due to the fluctuating electron clouds causing interactions between two atoms

Primary structure

A linear sequence of amino acids in a polypeptide

Held together by covalent bonds of the peptide backbone

The two ends of the structure are referred to as the Amino Terminus (N-Terminus) which is the start and the Carboxyl Terminus (C-terminus) which is the end

Determined directly from the gene corresponding to the protein

Nothing really going on here

Folding leads to secondary structure

Secondary structure

Highly regular local substructures of a protein

Three types: beta turn, beta sheet, and alpha helix

Beta turn

“u-turn”

The simplest secondary structure

Usually involving 3-4 residues

Polypeptide chain is forced to reverse direction making compact folding of the chain possible

Can make an incredibly small, sharp turn because of the hydrogen

Beta sheets

Two or more strands widely separated in the primary sequence orient side-by-side with hydrogen bonds between the strands

Held together by R groups interacting laterally

Forms an opening in the membrane, “porin”

Alpha helix

The most common secondary structural element

Can be right or left-handed

The R groups points out, so they can interact with each other

Tertiary structure

The folding of the secondary structural elements into a compact and nearly solid object stabilized by chemical bonding interactions (mostly electrostatic)

3-dimensional structure of a protein in space

ALL PROTEINS HAVE TERTIARY STRUCTURES

Quaternary structure

A three-dimensional structure of multi-subunit proteins and how those subunits stick together

Potassium ion channel protein

Made up of 4 polypeptide chains, but can be different number structures

NOT ALL PROTEINS HAVE QUATERNARY STRUCTURES

It can change its structure to interact

Three types of post-transcriptional modifications

Disulfide bridges, metal binding, bind of effector molecules

Disulfide bridge

Helps to stabilize and forms depending on the structure

-S-S oxidation of two sulfhydryl groups

Highly sensitive to the environment and is reversible

Not commonly found in intracellular proteins due to the reducing nature of the cytoplasm but very common in secreted proteins

Metal binding

Coordinated binding of a metal ion to several amino acid side chains in a single protein forming an internal metal chelate

Binding of effector molecules

Most important for stability is glycosylation

Other modifications can affect the conformation and function of the protein

Glycosylation

The addition of carbohydrates to specific amino acids, imagine a candied apple

Reversible modification

Turns proteins off or on

Ex: Phosphorylation and acetylation

Phosphorylation

Adds a phosphate group

Acetylation

Adds an acetyl group

Irreversible modifications

Ubiquitination and methylation

Ubiquitination

Adds a ubiquitin to a protein which tells the cell to degrade the protein

Methylation

Adds methyl group

Size-wise, where are motifs and domains

They’re in between secondary and tertiary

Types of protein motifs

Sequence, functional

Sequence motifs

Generally consist of a few structural elements relating primary structure to tertiary structure. Very small areas of 3D shape. So small that if you were to cut out a motif, then the protein falls apart

Functional/structural motif

A set of contiguous secondary structural elements that have a specific function.

Protein domains

A compact region of protein structure capable of stable folding independent of a large protein and having a specific function

Maintains its shape if it is cut out

Not up to tertiary structure

~40-~900 amino acids

Averaging ~200 amino acids

Have multiple domains