Week 2 Textbook Reading Flashcards
amino acid structure
All amino acids have the same basic underlying structure
Every AA has an alpha carbon to which all the other atoms and groups are attached
Every AA also has a carboxyl group which is OH-C=O
What differentiates AA
The R groups are the side chains and makes each AA unique
The linear order of how the AA are connected together is what gives rise to each unique protein
how is a peptide bond formed?
To form a peptide bond, there is a reaction between the carboxyl group and the amino group
R groups not involved in polypeptide formation
Rxn produces Amino end (N-terminus) and Carboxyl end (C-terminus)
how is a polypeptide chain formed?
Addition of AA and formation of peptide bonds is repeated until polypeptide chain is complete
While, maintaining polarity and directionality of the polypeptide
This is the primary structure
alpha helix
-secondary structure
-Backbone of alpha helix has a amino or N-terminal end and a carboxyl or C-terminal end
One AA are joined together into a polypeptide chain, now referred to as residues
Hydrogen bonding between an oxygen atom of the carbonyl group of residue “n” and the hydrogen atom of the amide group of the residue “n+4” on the same polypeptide chain, helps form the alpha helix
how is the cylindrical structure formed in an alpha helix?
When the hydrogen bonding between these groups is repeated in a regular fashion between residues, the peptide chain twists around on itself and forms a cylindrical structure
With enough regular repetition of the hydrogen bond formation, it produces a stable alpha helix that shows the characteristic 3-point amino acids
Since R groups aren’t involved in this process, thousands of proteins within the cell can have many alpha helices
amino acids and structure
Amino acids are small organic molecules with one defining property: they all possess a carboxylic acid group (-COOH) and an amino group (-NH2), both attached to a central a carbon atom
This a carbon also has a specific side chain, the identity of this is what helps us tell apart amino acids
why is that when AA are incorporated into a polypeptide chain, the charges on the functional groups are lost
In the cell, where the pH is close to 7, free amino acids exist in their ionized form; but, when they are incorporated into a polypeptide chain, the charges on their NH2 and -COOH groups are lost
describe the bonds and structure that make up proteins
The covalent bond b/w 2 adjacent AA in a protein chain is called a peptide bond, and the resulting chain of AA is called a polypeptide
Peptide bonds are formed by condensation rxns that link one AA to the next
The polypeptide always has as AA at one end-its N-terminus and a carboxyl group at its other end- its C-terminus
Always read starting from N-terminus
This difference in the 2 ends gives a polypeptide a definite directionality- a structural polarity
describe the D and L forms of AA
Like sugars, all AA (except glycine) exist as optical isomers called D and L forms
Only L forms are ever found in proteins (although D-amino acids occur as part of bacterial cell walls and in some antibiotics, and D-serine is used as a signal molecule in the brain)
peptide bonds
In proteins, AA are joined together by an amide linkage, called a peptide bond
Proteins are long polymers of AA linked by peptide bonds, and they’re written with the N-terminus toward on the left
Peptides are shorter, usually fewer than 50 AA long
The four atoms involved in each peptide bond form a rigid planar unit
There is no rotation around the C-N bond
disulfide bond
A disulfide bond can form b/w 2 cysteine (CH2-S) side chains in proteins
how enzymes promote intracellular chemical rxns
Enzymes promote intracellular chemical rxns by providing intricate molecular surfaces contoured with particular bumps that can cradle or exclude specific molecules
enzyme function and example
Catalyze covalent bond breakage or formation
Alcohol dehydrogenase, pepsin, DNA polymerase
structural protein function and example
Provide mechanical support to cells and tissues
Collagen and elastin
transport protein function and example
Carry small molecules or ions
Hemoglobin (carries oxygen), transferrin (carries iron)
motor protein function and example
Generate movement in cells and tissues
Myosin (provides force for humans to move), kinesin(interacts w/ microtubules to move organelles around cell)
storage protein function and example
Store AA or ions
Ferritin(stores iron in liver), casein(source of AA in milk for baby mammals)
signal protein function and example
Carry extracellular signals from cell to cell
Insulin(protein that controls glucose levels in the blood), netrin (attracts growing nerve cell axons to locations in developing spinal cord)
receptor proteins function and example
Detect signals and transmit them to the cell’s response machinery
Rhodopsin(retina detects light), insulin receptor (allows a cell to respond to the hormone insulin by taking up glucose)
transcription regulators function and example
Bind to the DNA to switch genes on or off
Lac repressor(in bacteria silences the genes for the enzymes that degrade the sugar lactose)
special purpose protein function and example
Highly variable
Antifreeze proteins of Arctic fish(protects their blood against freezing), green fluorescent protein from jellyfish (emits a green light)
how does a covalent peptide bond form?
A covalent peptide bond forms when the carbon atom of the carboxyl group of one AA shares electrons with the nitrogen atom from the amino group of a 2nd AA
Because a molecule of water is eliminated, peptide bond formation is classified as a
condensation reaction
polypeptide backbone structure
Because the 2 ends of each AA are chemically different- one end has an amino group (NH3+) and the other a carboxyl group (COO-)
Each polypeptide chain has directionality: the end carrying the amino group is called the amino terminus, or N-terminus, and the end carrying the free carboxyl group is the carboxyl terminus, or C-terminus
Projecting from the polypeptide backbone are the AA side chains- the part of the AA that’s not involved in forming peptide bonds
Side chains give each AA its unique properties
why are long polypeptide chains very flexible
Long polypeptide chains are very flexible as many of the covalent bonds that link the carbon atoms in the polypeptide backbone allow free rotation of the atoms they join
Therefore proteins can fold in many different way
The shape of each folded chain is constrained by many sets of weak noncovalent bonds that form within proteins
what are the bonds that help proteins fold and maintain their shape
The noncovalent bonds that help proteins fold up and maintain their shape are the hydrogen bonds, electrostatic attractions and van der Waals attractions
Because a noncovalent bond is much weaker than a covalent bond, it takes many noncovalent bonds to hold 2 regions of a polypeptide chain tightly together
The stability of each folded shape is largely determined by the combined strength of large numbers of noncovalent bonds
hydrophobic force
In an aqueous environment, hydrophobic molecules, including the nonpolar side chains of particular AA, tend to be forced together to minimize their disruptive effect on the hydrogen-bonded network of the surrounding water molecules
An important factor governing the folding of any protein is the distribution of its polar and nonpolar amino acids
The nonpolar (hydrophobic) side chains tend to cluster in the interior of the folded protein
Tucked away inside the folded protein, hydrophobic side chains can avoid contact with the aq. environment that surrounds them inside a cell
how is a conformation of a polypeptide chain determined
The final folded structure, or conformation, adopted by any polypeptide chain is determined by energetic considerations: a protein generally folds into the shape in which its free energy (G) is minimized
The folding process is thus energetically favourable, as it releases heat and increases the disorder of the universe
denaturation
A protein can be unfolded, or denatured, by treatment with solvents that disrupt the noncovalent bonds holding the folded chain together
This converts the protein into a flexible polypeptide chain that has lost its natural shape
When the denaturing solvent is removed, and the proper conditions are provided, the protein often refolds spontaneously into its original conformation→ renaturation
chaperone proteins
Protein folding in a living cell is generally assisted by a large set of special proteins called chaperone proteins
Some of these bind to partly folded chains and help them to fold along the most energetically favourable pathway
isolation chambers
Others form “isolation chambers” where single polypeptide chains can fold without the risk of forming loose material in the crowded conditions of the cytoplasm
This system also requires an input of energy from ATP hydrolysis, mainly for the association and subsequent dissociation of the cap that closes off the chamber
backbone model of a protein
Backbone model: shows the overall organization of the polypeptide chain and provides a straightforward way to compare the structures of related proteins
ribbon model
Ribbon model: shows the polypeptide backbone in a way that emphasizes its folding patterns
wire model
includes the positions of all the AA side chains
This view is useful for predicting which AA might be involved in the protein’s activity
Space-filling model
Space-filling model: provides a contour map of the protein surface, which reveals which AA are exposed on the surface
Also shows how the protein might look to a small molecule such as water or to another macromolecule in cell
alpha helix
a helix was the first folding pattern to be discovered and was found in the protein a-keratin
beta sheet
B sheet was found in the protein fibroin, the major part of silk
Both result from hydrogen bonds that form between the N-H and C=O groups in the polypeptide backbone
Because the AA side chains aren’t involved in forming these hydrogen bonds a helices and B sheets can be generated by different AA sequences
how is the alpha helix made?
The a helix is generated when a single polypeptide chain turns around itself to form a structurally rigid cylinder
A hydrogen bond is made b/w every 4th AA, linking the C=O of one peptide bond to the N-H of another
This pattern gives rise to a regular right-handed helix
structure of polypeptide backbone
The polypeptide backbone, which’s hydrophilic, is hydrogen-bonded to itself inside the a helix
Here it’s shielded from the hydrophobic lipid environment of the membrane by protruding nonpolar side chains
Sometime 2 or 3 a helices will wrap around one another to form a stable structure called a coiled-coil
This structure forms when the a helices have most of their nonpolar (hydrophobic) side chains along one side so they can twist around each other with their hydrophobic side chains facing inward
This minimizes contact with the aq cytosol
beta sheet structure (segments)
B sheets form rigid structures at the core of many proteins
B sheet is made when hydrogen bonds form between segments of a polypeptide chain that lie side by side
When the neighbouring segments run in the same orientation (e.g. N-terminus to C-terminus), the structure forms a parallel B sheet
When they run in opposite directions, the structure forms an antiparallel B sheet
amyloids
Misfolded proteins can form amyloid structures that can cause disease
When proteins fold incorrectly, they sometimes form amyloid structures that can damage cells and even whole tissues
These amyloid structures are thought to contribute to a number of neurodegenerative disorders, including Alzheimer’s, Parkinson’s and Huntington’s disease
why is the brain vulnerable to damage?
Because most neurons can’t regenerate, the brain is vulnerable to the damage caused by a buildup of amyloid aggregates
prions
Other neurodegenerative disorders like “mad cow” disease in cattle or scrapie in sheep are caused by misfolded proteins called prions
Prions are considered infectious because the amyloid form of the protein can convert properly folded molecules of the protein into the abnormal, disease-causing conformation
These infections occur when tissues containing prions are introduced into the food chain
After being eaten, the misfolded prions can find their way to the brain, where they form aggregates that spread rapidly from cell to cell → causing the death of the affected animal or human
primary structure
Because a protein’s structure begins with its AA sequence, this is considered its primary structure
secondary structure
The next level of organization includes the a helices and B sheets that form within certain segments of the polypeptide chain; these folds, produced by hydrogen bonding within the polypeptide backbone, are elements of the protein’s secondary structure
tertiary structure
The full 3D conformation formed by an entire polypeptide chain including the a helices, B sheets and all other loops and folds that form b/w the N- and C- termini is referred to as its tertiary structure
Heavily influenced by the many weak, noncovalent bonds that form along the polypeptide chain, b/w AA side chains and b/w side chains and the polypeptide backbone
quaternary structure
If the protein molecule exists as a complex of more than one polypeptide chain, then these interacting polypeptides, held together by noncovalent bonds, form its quaternary structure
protein domain
This organizational unit is the protein domain, which is defined as any segment of a polypeptide chain that can fold independently into a compact, stable structure
how can an extended protein filament be produced
A chain of identical protein molecules can be formed if the binding site on one protein molecule is complementary to another region on the surface of another protein molecule of the same type
Because each protein molecule is bound to its neighbour in an identical way, the molecules will often be arranged in a helix that can be extended indefinitely in either direction
This can produce an extended protein filament
globular proteins
where the polypeptide chain folds up into a compact shape like a ball with an irregular surface
E.g. enzymes
fibrous proteins
Fibrous proteins→ these proteins are elongated with a rod like shape such as collagen or a keratin filament
coiled coil formation
An a-keratin molecule is a dimer of 2 identical subunits, with the long a helices of each subunit forming a coiled-coil
These coiled-coil regions are capped at either end by globular domains containing binding sites that allow them to assemble into ropelike intermediate filaments
This is a component of the cytoskeleton that gives cells mechanical strength
covalent cross-linkages
Extracellular proteins are often stabilized by covalent cross-linkages
To help maintain the structures of some proteins, the polypeptide chains are often stabilized by covalent cross-linkages
These can tie together 2 AA in the same polypeptide chain or join together many polypeptide chains in a large protein complex
The most common cross linkages in proteins are sulfur-sulfur bonds
These disulfide bonds are used to reinforce a secreted protein’s structure or to join 2 different proteins together
They don’t change a protein’s conformation, but instead act as a sort of “atomic staple” to reinforced the protein’s most favoured conformation
How can the changes in shape experienced by proteins be used to generate such orderly movements?
A protein that’s required to walk along a cytoskeletal fiber can move by undergoing a series of conformational changes
However, with nothing to drive these changes in one direction or the other, the shape changes will be reversible and the protein will wander randomly
To force the protein to move in one direction, the conformational changes must be unidirectional
-To achieve this, one of the steps must be made irreversible
-E.g. by coupling one of the conformational changes to the hydrolysis of an ATP molecule that’s tightly bound to the protein
scaffold proteins
Many interacting proteins are brought together by scaffolds
Many protein complexes are brought together by scaffold proteins, large molecules that contain binding sites recognized by multiple proteins
By binding a specific set of interacting proteins, a scaffold can greatly enhance the rate of a chemical rxn or cell process
These proteins cluster under the plasma membranes of communicating nerve cells, allowing them both to transmit and to respond to the appropriate messages when stimulated to do so
biomolecular condensate
Biomolecular condensate→ a large aggregate of phase-separated macromolecules that creates a region with a special biochemistry without the use of an encapsulating membrane
Each condensate contains at least one type of scaffold protein or scaffold RNA molecule that can interact with other molecules called clients, which become concentrated there
phase interaction
Phase interaction → a property where a network of weak interactions allows individuals allows individual molecules to come and go, while the condensate as a whole remains intact and separated from its surroundings
chromatography
To isolate the desired protein, the standard approach involves purifying the protein through a series of chromatography steps, which use different materials to separate the individual components of a complex mixture into portions
The most efficient forms of protein chromatography separate polypeptides on the basis of their ability to bind to a particular molecule, a process called affinity chromatography
electrophoresis
Proteins can also be separated by electrophoresis
In this technique, a mixture of proteins is loaded onto a polymer gel and subjected to an electric field
mass spectrometry
A faster way to determine the AA sequence of proteins that have been isolated from organisms for which the full genome sequence is known is a method called mass spectrometry
Sensitive technique that enables the determination of the exact mass of each of the molecules in a complex mixture