CHEM 53.10 - Levels of Protein Structures

What does the primary structure of proteins describe?

It describes the sequence of amino acid residues.

What does the secondary structure of proteins describe?

It describes the localized conformation of the polypeptide backbone.

What does the tertiary structure of proteins describe?

It describes the 3-D structure of an entire polypeptide, including all side chains.

What does the quaternary structure of proteins describe?

It describes the spatial arrangement of polypeptide chains in a protein with multiple subunits.

Why do we need different levels to describe protein structure?

The different levels describe different aspects of covalent connections and folding patterns arising from intermolecular forces.

Why is the primary structure of proteins necessary?

Because all information on protein shape and function arises from the amino acid sequence

What does the primary structure not tell us?

It does not give a clear picture of the localized structures that can be found in a protein or what the general 3-D shape of a protein is.

This is the covalent structure of a polypeptide.

Primary Structure

This specifies the covalent structure of a polypeptide.

Sequence of amino acid residues

In the primary structure, why is it important for the sequence of a polypeptide to be known?

If the sequence is known, then all the other atoms that are covalently linked will also be known.

The amino acid sequence of peptides contains this type of information.

Information that is necessary for folding the peptide into its "native" structure

How are polypeptides named?

They are named according to the amino acid sequence, following the N -> C orientation.

Aside from the sequence itself, what other information does the primary structure provide?

Regions of significant similarities between two compared sequences, as well as evolutionary relationships between organisms

These are the basic classifications of secondary structures in polypeptides.

α-helices and β-strands

How many levels of organization are exhibited by protein structures?

4

These are the levels of organization exhibited by protein structures.

Primary, Secondary, Tertiary, Quaternary

These protein structures describe localized backbone conformations of a polypeptide.

Secondary Structures

How many types of secondary structures are present in polypeptides?

2

With respect to each other, what makes secondary structures localized?

They involve residues that are relatively near each other in the sequence.

This can be characterized via spatial relationships between backbone atoms.

Backbone Conformation

This plane traverses two amino acids and arises from the partial double-bond character of the peptide bond connecting them.

Amide Plane

What is the significance of secondary structures towards polypeptide backbones?

They satisfy H-bonding requirements of the backbone atoms.

Under physiological conditions, how does a polypeptide chain "react" to satisfy H-bonding requirements?

Folding in different ways as a result of "wanting" to H-bond

These limit the possible conformations a polypeptide backbone can assume.

Geometric and steric constraints around its peptide bonds

This type of rotation is exhibited by peptide bonds, which restricts the folding possibilities of a polypeptide.

Hindered Rotation

How can H-bonding requirements between polypeptides be satisfied as much as possible, despite steric and geometric constraints?

By adopting two major conformations, the α-helix and β-sheet

This is the handedness exhibited by α-helices.

Right-Handed

How many residues make up a complete turn of an α-helix?

3.6 residues

This is the vertical distance between successive residues of an α-helix.

1.5 Å

How high is the helical pitch of α-helices?

5.4 Å

These are the four specific characteristics of α-helices.

Substantial dipole moment, Stabilized by very specific, intrachain H-bonds, Side chains projected outward from the helix axis, Amphipathic

Describe the substantial dipole moment of α-helices.

It has a partial positive charge at the N-terminus and a partial negative charge at the C-terminus.

In the context of α-helices, where do negatively-changed molecules frequently bind to proteins?

Near the N-terminus of an α-helix

These stabilize the structure of an α-helix.

Very specific, intrachain hydrogen bonds

Describe the orientation of the peptide (amide) planes of an α-helix relative to the helix axis.

Approximately parallel

Describe the H-bonding pattern that manifests in α-helices.

A very regular H-bonding pattern where a carbonyl O of a residue "i" will H-bond with the amino hydrogen 4 residues up the chain (i+4)

In the structure of α-helices, what direction are the carbonyls facing?

Upwards

In the structure of α-helices, what direction are the amino hydrogens facing?

Downwards

How many residues make up an α-helix?

12 residues

In what direction are the side chains of the residues of an α-helix projected?

Outwards from the helix axis at 100° intervals

Is the center of an α-helix solid or hollow?

Solid

Viewing through the helical axis, how many degrees separate two consecutive residues from each other?

100° per residue

This representation is often used to visualize the placement of consecutive amino residues as viewed through the helical axis.

Helical Wheel Diagram

This is the primary purpose of the helical wheel diagram.

It enables us to see how the placement of the residues affects the polarity/hydrophobicity of an α-helical region.

This property of an α-helix is characterized by it having both polar and nonpolar sides in its structure.

Amphipathic

These are two examples of proteins that are composed of purely α-helical secondary, structural components.

Myohemerythrin and β-hemoglobin subunits

These are the other less abundant types of helical structures found in proteins.

3_10-helices and π-helices

These structures are made up of β-strands.

β-sheets

These make up the structures of β-sheets.

Aligned β-strands of polypeptide whose H-bonding requirements are met by bonding between neighboring strands

Which of the two secondary structures of proteins is more extended?

β-strands

How far apart are neighboring residues in a β-strand?

3.5 Å

What type of H-bonding is manifested in β-sheets?

Inter-strand H-bonding

This structure is formed by H-bonding between two β-strands that are lying next to each other.

β-sheet

Do α-helices and β-sheets manifest the same type of H-bonding in their structures? Why or why not?

No. H-bonding in α-helices is intra-chain while it is inter-strand in β-sheets.

These are the two possible arrangements that β-sheets can be aligned in.

Antiparallel and Parallel

This arrangement of β-sheets features strands that run in opposite directions.

Antiparallel

In antiparallel β-sheets, which groups (present between partner amino acids of the different strands) H-bond together?

The NH and CO groups of each amino acid on one strand H-bonds with the CO and NH groups, respectively, with its partner amino acid on the other strand.

This arrangement of β-sheets features strands that run in the same direction.

Parallel

Describe the H-bonding pattern in parallel β-sheets.

The NH group of a residue "i" in Strand 1 is H-bonded to the CO group of an amino acid "i-1" on the adjacent Strand 2. The CO group of residue "i" on Strand 1 is H-bonded to the NH group of an amino acid "i+1" in Strand 2 (two residues away from the CO group of residue "i-1").

This is the shape of the structure, and therefore the successive amide planes, of β-sheets.

Pleated Structure

What causes β-sheets to have a pleated appearance?

The tetrahedral Cα atoms found in the folds of the pleats

This is the other term used to refer to β-sheets.

β-pleated sheets

How are amino acid residues in β-sheets projected?

Alternately from each side of the sheet plane

How many β-strands does a single β-sheet contain?

2 to more than 12 strands, with an average of 6 strands

On average, how many residues make up a β-strand?

6 residues

This property of amino acids allows us to predict well the types and structures of major secondary structures in proteins.

Varied propensities for α-helix and β-sheet formation

α-helices and β-strands are often found to be connected by these structures that abruptly change direction.

Turns and Loops

This type of structure connects two antiparallel β-strands.

Short (Reverse) Turn

This type of structure connects two parallel β-strands.

Longer Loop

What do reverse turns between β-strands do?

They reverse the direction of the polypeptide backbone.

How many residues comprise a β-turn?

4

Why are β-turns named as such?

Because they connect consecutive β-strands together

What characterizes and stabilizes the structure of β-turns?

The H-bonding pattern exhibited in the turn.

Which groups H-bond to form a β-turn?

The peptide chain forms a tight loop with the carbonyl oxygen of one residue that H-bonds with the amide hydrogen of the residue three positions down the chain.

These two amino acids are frequently found in β-turns.

Proline and Glycine

This amino acid frequently disrupts secondary structures.

Proline

What causes proline to disrupt secondary structures?

It lacks an amino hydrogen that can participate in H-bonding. As a result, proline is prevented from participating in the H-bonding requirements of α-helices and β-sheets.

The presence of proline makes the formation of these structures favorable.

β-turns

These are taken to mean any other "secondary" structure that does not have a regular or characteristic geometric properties.

Coils / Random Coils

What makes random coils in proteins more unordered?

There is more conformational flexibility in stretches of coils.

This property allows stretches of coils to interact with water, ligands, or other proteins.

Lack of intra-strand and inter-strand non-covalent interactions such as H-bonding

This protein structure describes the overall conformation of a protein.

Tertiary Structure

The tertiary structure describes this specific arrangement of atoms in proteins.

Global arrangement of ALL atoms in a protein

The tertiary structure includes this aspect of amino acid sequences.

Long-range aspects wherein amino acids distant in the sequence can be brought closer together.

This is the primary difference between the secondary and tertiary structures of proteins.

Secondary structures characterize the spatial arrangement of residues that are relatively close in the sequence. Tertiary structures describe the global arrangement of all atoms and sequences of a protein, including the long-range aspects.

If a protein can be described as a collection of secondary structures, how do we describe the tertiary structure of the protein from this?

The way the secondary structures pack closely to form the 3-D structure of the protein.

This structure allows proteins to be classified into broad structural categories.

Tertiary Structure

These properties of the tertiary structure of proteins classify them into four major classes.

General shape and secondary structure composition

These are the four major classes of proteins according to their tertiary structure.

Globular, Fibrous, Membrane, Intrinsically-Disordered

According to their tertiary structure, is it possible for proteins to be classified into more than one category?

Yes. Some proteins have segments that fall into two or more of these categories.

These proteins are compactly folded polypeptides.

Globular Proteins

As a result of compact folding, what is the general shape of (most) globular proteins?

Roughly spheroidal shape

What structures can compose a globular protein?

A mixture of secondary structures exhibiting formation of turns and loops

What allows compact folding in globular proteins to occur?

The formation of turns and loops which allows for the polypeptide chain to change direction multiple times

Name an example of a globular protein.

Ras protein

Generally, are globular proteins soluble in water?

Yes, most globular proteins are water-soluble as they have a hydrophilic exterior and a hydrophobic interior.

These proteins are large, elongated molecules.

Fibrous Proteins

What structures compose a fibrous protein?

Long polypeptide chains consisting of long strands or sheets that are organized approximately parallel along a single axis

This property is exhibited by long polypeptide chains in fibrous proteins to form thicker structures.

Aggregation

These are mechanically strong proteins that play a structural role in cells.

Fibrous Proteins