Proteins: Tertiary Structure Overview

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Questions and Answers

What is primarily responsible for the stability and complexity of proteins?

The packing of secondary structural elements onto one another (correct)

The presence of multiple active sites within the protein

The formation of disulfide bonds between cysteine residues

The order of amino acids in the primary structure

Which characteristic is commonly found in the majority of proteins' structures?

A high degree of symmetry in the fold

A single layer of secondary structure elements

Randomly arranged polypeptide chains

A hydrophobic core with tightly packed secondary structures (correct)

What role do combined secondary structure elements play in proteins?

They reduce the overall flexibility of the protein

They primarily determine the primary structure of the protein

They contribute to creating extended protein surfaces (correct)

They limit the binding capacity of the protein

What was noted about the complexity of myoglobin's structure in 1958?

It exhibits a remarkable lack of symmetrical regularities Signup and view all the answers

How many layers of secondary structure elements do most proteins typically have?

2-5 layers Signup and view all the answers

What role do hydrophobic residues typically play in protein structure?

They are generally buried in the protein core. Signup and view all the answers

Which of the following best describes the positioning of loops and turns in proteins?

They are generally surface exposed. Signup and view all the answers

Why are polar residues more commonly found on the surface of proteins?

They help in solubilizing the protein by interacting with water. Signup and view all the answers

What characterizes the water's interaction with proteins?

Water is crucial for protein folding and function. Signup and view all the answers

Which statement about the arrangement of secondary structures in proteins is most accurate?

Secondary structures can contribute to hydrogen bonding. Signup and view all the answers

What is a characteristic of structural waters in proteins?

They are consistently found in specific positions within the protein. Signup and view all the answers

What is the consequence of proteins being unable to fold or function in a vacuum?

The solvent plays a significant role in their structure and behavior. Signup and view all the answers

What is the primary purpose of surface-exposed hydrophilic residues in proteins?

To interact with water and aid in solubilization. Signup and view all the answers

What structural feature is primarily used by globins to bind to a heme cofactor?

a-helices Signup and view all the answers

At what angles do the helices in globins generally cross each other?

20° and 50° Signup and view all the answers

What type of protein structure is commonly shown in topology diagrams?

Multi-spanning TM protein Signup and view all the answers

What does a topology diagram primarily represent?

The organization of a protein's secondary structure Signup and view all the answers

Which statement about globins is true?

Globins are a diverse group of monomeric proteins. Signup and view all the answers

Which of the following best describes the positioning adjustments made by side chains in globins?

They adjust to enhance their fit. Signup and view all the answers

What do adjacent arrows in a topology diagram represent?

Part of the same b-sheet Signup and view all the answers

What aspect of proteins do topology diagrams not represent?

The lengths of helical segments Signup and view all the answers

What is a key characteristic of the horseshoe fold protein structure?

It contains a repeating ~30 residue motif. Signup and view all the answers

In a fully extended state, how much does a protein stretch per residue?

$3.5 Å$ Signup and view all the answers

What is the average size of a human protein in amino acids?

375 a.a. Signup and view all the answers

What defines peptides in terms of amino acid length?

Less than 50 amino acids. Signup and view all the answers

How much can a flexible protein linker of 100 amino acids stretch at most?

350 Å Signup and view all the answers

Which statement is true regarding the size of proteins in bacteria compared to humans?

Bacteria have fewer large proteins than humans. Signup and view all the answers

What is the diameter of a small protein complex with 100 amino acids?

3 nm Signup and view all the answers

How many times does the volume of an oligomer increase as the number of amino acids doubles?

What characteristic sequence repeat is commonly found in coiled-coil domains?

Heptad repeat Signup and view all the answers

In coiled-coil structures, which residues typically interact at the center of the complex?

a with a' and d with d' Signup and view all the answers

What is the average number of residues per turn in an alpha-helix?

3.6 Signup and view all the answers

What role do the 'e' and 'g' residues play in coiled-coil structures?

They stabilize the structure through electrostatic interactions. Signup and view all the answers

What term describes the way residues fit together in a coiled-coil structure?

Knobs into holes Signup and view all the answers

Which amino acid is most commonly associated with the 'knobs' in coiled-coil structures?

Leucine Signup and view all the answers

What is the significance of the pattern of charged residues in coiled-coil proteins?

It helps specify interaction partners for coiling. Signup and view all the answers

What structural advantage does the helical packing provide in coiled-coils?

It allows for predictable interactions through sequence repetition. Signup and view all the answers

What prediction did Francis Crick make about coiled-coils?

They would be a stable structural motif. Signup and view all the answers

Which of the following is an application of coiled-coils in biological systems?

Transcription factor dimerization Signup and view all the answers

Study Notes

Tertiary Structure

Secondary structure elements are generally not stable enough to persist in solution
Proteins use packing of secondary structure elements onto one another to achieve stability and complexity
Combining multiple structural elements allows extended protein surfaces to be built
These then can then evolve the flexibility, binding complementarity and overall complexity required for most protein functions

Typical Organization of Proteins

The majority of amino acids are found in either a-helices or b-strands
These elements generally pack tightly together, with a hydrophobic core formed between them
Most proteins have 2 – 5 “layers” of secondary structure elements (e.g.b-b; a-b-a; a-a; a-b-b-a)
About a third of all residues are typically in turns or loops

Organization of Proteins Surface Exposure

Helices are generally at least partially surface exposed in soluble proteins
b-strands can be fully buried
Loops and turns (connecting secondary structure elements) are almost always surface exposed
This reflects the need for water to make hydrogen bonds to unpaired backbone groups

Hydrophobic Residues Dominate the Protein Interior

Non-polar residues are generally packed together in the core of the protein
This hydrophobic core maximizes the hydrophobic effect
Polar residues are cover most (but not all) of the solvent exposed surface of protein
Here they interact with water, helping solubilize the protein
Relatively few polar residues are buried; if they are, they almost always hydrogen bond with the backbone

The Solvent Environment Drives Protein Structure

Proteins can neither fold nor function in a vacuum
Their behaviour cannot be understood independent of the medium they are dissolved in
Solvent properties of water are dominated by its polar character, its strong tendency to form hydrogen bonds and by its relatively ordered structure
Water makes strong interactions with non-polar residues on the protein’s surface

Water Forms an Integral Part of a Protein’s Structure

Waters are bound all over the surface of a protein molecule
Some water molecules are also found deeply buried in the structure
These water molecules are essentially always found in the given position in the molecule
They are an integral part of the structure

Globins

Globins are a diverse group of a-helical proteins
The structure is built by wrapping eight a-helices around a heme co-factor
The helices in globins generally cross at ~20° or 50° angles where they pack against one another
Individual side chains adjust their positions to maximize their fit
The sequence is also evolved to optimize fitting between elements

“Typical” Average Sized, Monomeric Proteins

Proteins show massive diversity in their organization
Most proteins however share the overall organization of their structure with many other proteins, including ones very distantly related
These protein folds acquire specific names that form part of the basic vocabulary of structural biology

Topology Diagrams

A topology diagram is a flat representation of the organization of a protein’s secondary structure
b-strands are shown as arrows; adjacent arrows are part of the same sheet
Helices are generally shown as rectangular boxes
Loops are shown as lines connecting secondary structure units
Only the arrangement of elements are significant - not lengths
Topology diagrams show a protein’s overall architecture in 2D

Multi-Spanning TM Protein Topology

For transmembrane helical proteins, topology diagrams are used to indicate the location of extracellular and intracellular loops, location of modifications, etc.

Helix-Helix Packing in Coiled-Coils

a-helices average 3.6 residues per turn
Packing two helices side by side results in a pattern of interactions that almost repeats every seven residues
Wrapping two helices around one another with a slight left-handed twist produces a repeat of exactly seven (2 x 3.5) residues
This allows (variants of) a seven residue repeat sequence to be used over and over to create long fibers with a 140 Å super-helical repeat

Coiled-Coils Show a Heptad-Repeat Organization

Coiled coil domains show a characteristic heptad repeat
Residues are labeled “a” - “g”
In the adjacent helices, a interacts with a’ and d with d’ in the center of the complex
“d” is small and hydrophobic, generally Leucine

“Knobs Into Holes” Packing

Where four residues in three turns of one helix form a “hole” that a mid sized hydrophobic residue or “knob” can fit nicely into
Note that this is a variant of ridges-into-grooves packing, but extended by the helices wrapping around one another
Francis Crick predicted that coiled-coils would be a stable structural motif in 1953 (3 years before the first protein x-ray structure!)

Coiled-Coils = Leucine Zippers

In coiled coils the “knobs” are most commonly leucine residues
Hence the “leucine zipper” name given to short coiled coils used to dimerize some transcription factors

Electrostatic Stabilization in Coiled Coils

The hydrophobic core of coiled-coils is relatively small, so stabilization by electrostatic interactions is unusually important
Residues in the “e” and “g” positions are often charged and complementary
The pattern of charged residues can help specify who should coil with who (homo and hetero-dimers)

Coiled Coils Play Diverse Roles

Coiled-coils are useful as a relatively small motif can drive protein interactions

a/b Horseshoe Fold

These proteins are characterized by a repeating ~30 residue motif with seven conserved leucine residues
This fold resembles an extended ab barrel except that it is open
One side of the b-sheet is buried under helices, the other is exposed to solvent
Because helices are bulkier than sheets, these proteins curve strongly

Protein Metrics (1)

Ca-Ca distances in trans conformation are ~3.8 Å
In a fully extended state, protein stretch 3.5 Å per residue (as the chain zig-zags)
E.g.a 100 a.a.flexible protein linker can stretch at most 350 Å (or 35 nm)
An a-helix stretches around 1.5 Å per residue (more compact)

Protein Metrics (2)

A small protein complex (100 a.a.) forms a roughly spherical body about 3 nm in diameter, a largish one (1000 a.a.) about 7 nm
For oligomers, this includes all subunits
Eight (23) times the number of amino acids doubles the volume
The largest structured cellular objects (e.g.large viruses, vaults, gas vesicles) can reach ~1000 nm (1 µm) in length

Protein Metrics (3)

Translated, functional polypeptides encoded in the human genome range from 6 a.a.to 30,000 a.a.long
The average size of a human protein is 375 a.a. Few proteins are larger than 1,000 a.a. Bacteria have even fewer large proteins, and their average protein is 100 a.a.smaller

Small Proteins (a.k.a. Peptides)

Peptides are simply small proteins – typically defined as being less than 50 amino acids
Peptides as short as six amino acids have been shown to be translated and be functional
Peptides are often cut from longer proteins (zymogens) by proteolysis

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Description

Explore the intricacies of protein tertiary structure and its significance in achieving stability and complexity through secondary structure elements. This quiz covers typical organization patterns, the role of amino acids, and the exposure of various structures within proteins. Test your knowledge on the fundamental aspects of protein organization and functionality.