Protein Structure Flashcards
A protein molecule = () of aas linked by an () bond (also named () bond)
Condensation reaction between () of one aa and () of another : () is lost to form an () bond called ()
Resulting structure is ()
() is composed of 4 amino acid and () peptide bonds
() of the peptide has free electrons that are not involved in () and can potentially participate in ()
polymer, amide, peptide.
amino, carboxyl, water molecule, amide, peptide.
dipeptide, tetrapeptide, 3, nitrogen, bonding, hydrogen bonding.
There is a certain sense of () for peptide bond
Resulting peptide has a free () + ()
First always to () and second always to the ()
Nitrogen of peptide bond has free electrons that are not available all the time, meaning that they are not () (amide is a () bond) and will not contribute to () on the protein (not () )
Peptide bond has a () bond character we know from organic that alkenes have a planar shape where all substituent on C=C, in this case C=N lie within the same plane.
In addition a double bond may assume a () or () .
Peptide bond is () that is the () is () oriented with the () (always)
direction, amino terminus and carboxyl terminus, first to the left and second to the right.
deprotonated, neutral, charge, ionizable.
double, cis or trans.
trans peri planar, NH, oppositely, carbonyl
example of aa that favors cis isomer: ()
Cis: 2R groups are close to each other creating (), () the structure.
proline, steric hindrance, destabilizing
Restricted rotation between the () and the () of the peptide bond
Rotation is permissible around certain angles like () angle () , and () . These rotations will allow the R groups to rotate in space about a () maximizing the favorable interaction between the () in the protein molecule.
Their importance identified by () who studied () + the best () of synthetic () while () polypeptide chains about the permissible angles psi and phi
This allowed him to describe the () possible favorable structures that aa in polypeptide may assume.
carbonyl and NH
phi, between c alpha and NH and psi between c alpha and c=o.
specific angle, different R groups, ramachandran, shape, conformation, polypeptides, rotating, sterically.
Change in () (polarity, ionic strength, proton concentration) influences the () and () of protein which results from () of certain interaction or () new interactions that can include () or () forces.
First: () -bonding (() containing aa or amide).
() interactions (() /() bridges occurring between () and () aa).
() interactions (() () R groups).
() interaction or bond other than the peptide bond we have () () that result from () of () residues. (This involves the conversion of the () (-() ) groups in () to () (() ) bonds, typically through the () of electrons. This process is not covalent but rather involves the formation of covalent disulfide bonds, which are a type of covalent bond formed between sulfur atoms.)
environment, conformation, function, changing, creating, non covalent, covalent
H-bonding, OH
ionic, electrostatic, salt, acidic, basic
hydrophobic, water insoluble,
covalent, disulfide bridges oxidation cysteine, thiol SH to disulfide S-S loss
PRIMARY STRUCTURE: LINEAR SEQUENCE FROM N TO C TERMINALS SIGNIFICANCE
Physical protein property : () , possible location (presence of () ) for instance mitochondrial proteins have () and () rich sequences that will be recognized by mitochondrial machineries directing protein into mitochondria.
Knowledge of sequence of active sites helps in elucidating () and ()
Identifying the sequence helps in relating sequence to ()
A simple alteration in one aa out of the entire protein may change the () (normal () vs sickle () ). But does this mean that protein sequence is absolutely invariant or constant? NO
Proteins are () so we may have aa variations with little or no effect on function. When we say that, it means that they can exist in multiple structural forms or conformational states, often with distinct functions or properties.
Note that we may have same protein with many alternatively () translated in different organs. example: Many () of () are translated in different organs, these have different sequences and primary structures but carry on the same function (() )
One can identify () proteins for instance if you have isolated it and identified its sequence, comparing it to other well () proteins with known function, a plausible function for this protein may be proposed.
Comparing primary structure is commonly used to predict () in structure and function between proteins.
2 sequences are () if they are highly alignable, (if they share a high degree of structural and sequence similarity, making them align well with each other in a meaningful way), usually evolving from the same gene. In addition the sequence may allow us to deduce () relationship between organisms. Comparing different species homologous proteins which are evolutionary related, perform the same function in different species.
For example the primary structure of () , an electron () in () , was determined in () diff species. In all of them, invariant () aa sequence was detected indicating that these are important for biological activity.
Current protein data base:
()
()
PRIMARY STRUCTURE: LINEAR SEQUENCE FROM N TO C TERMINALS
Physical protein property : polarity hydrophobicity, solubility, possible location (presence of targeting sequencing) for instance mitochondrial proteins have lysine and arginine rich sequences that will be recognized by mitochondrial machineries directing protein into mitochondria.
Knowledge of sequence of active sites helps in elucidating mechanism and mode of action.
Identifying the sequence helps in relating sequence to pathology.
A simple alteration in one aa out of the entire protein may change the function (normal hemoglobin vs sickle hemoglobin). But does this mean that protein sequence is absolutely invariant or constant? NO
Proteins are polymorphic so we may have aa variations with little or no effect on function. When we say proteins are polymorphic, it means that they can exist in multiple structural forms or conformational states, often with distinct functions or properties.
Note that we may have same protein with many alternatively spliced transcripts translated in different organs. Many isozymes of lactate dehydrogenase are translated in different organs, these have different sequences and primary structures but carry on the same function (conserved active site)
One can identify new proteins for instance if you have isolated a new protein and identified its sequence, comparing it to other well defined proteins with known function, a plausible function for this protein may be proposed.
Comparing primary structure is commonly used to predict similarity in structure and function between proteins.
2 sequences are homologous if they are highly alignable, (if they share a high degree of structural and sequence similarity, making them align well with each other in a meaningful way), usually evolving from the same gene. In addition the sequence may allow us to deduce evolutionary relationship between organisms. Comparing different species homologous proteins which are evolutionary related, perform the same function in different species.
For example the primary structure of cytochrome c, an electron carrier in the electron transport chain, was determined in 60 diff species. In all of them, invariant 27 aa sequence was detected indicating that these are important for biological activity.
Current protein data base:
EMBL : European Molecular Biology Laboratory Data Library
PIR : Protein Identification Resource sequences Data Base
One can deduce the protein sequence from the () sequence however, you must keep in mind that very often there are some () occurring, the information of which mat not be deduced from the gene sequence.
So one has to combine both () and () ways to determine the protein sequence.
Moreover the location of () is not possible predictable form gene sequence. One has to refer thus to both()
One can deduce the protein sequence from the gene sequence however, you must keep in mind that very often there are some posttranslational modification occurring, the information of which mat not be deduced from the gene sequence.
So one has to combine both genetic and classical ways to determine the protein sequence.
Moreover the location of disulfide bridges is not possible predictable form gene sequence. One has to refer thus to both classical enzymatic and chemical ways and molecular.
- In the secondary structure of proteins, regular structural () are characterized by () interactions between neighboring () that result in repetitive and predictable patterns, such as a() or () , contributing to the overall () -dimensional structure of the protein.
- Secondary structure refers to regular () of the protein.
The local () of polypeptide into () structures or () that result from () between the peptide bonds.
Combinations of phi and psi angles that result in () structures between () atoms are not allowed.
repeats, short-range, amino acids, alpha helix, beta pleated sheets, 3.
folding, folding, periodic, repeats, H-bonding, sterically hindered, non-bonded
Alpha helices () secondary structure and are present in both () and () (variable %)
For example both globular proteins () and () are mainly composed of a() (80%) however () (proteolytic enzyme) is completely devoid of ()
Moreover some () proteins have high content of alpha helix such as () and () .
Here we are dealing with short range () H-bonding interactions between peptide bond () and () (first () second () ).
() structure made of () residues to ()
This will cause the backbone of the polypeptide to () , around imaginary () , by an () amount forming a () . Assuming () case shape.
Each alpha helix has approximate () residues per turn, with H-bonded peptide bonds directed () to the imaginary axis while the R groups of the side chain are () to the outside surface avoiding () or interference.
Extensive tightly packed H-bonding in the inner core () the alpha helix.
Some alpha helixes have both () and () sides (() )
Alpha helices most common secondary structure and are present in both globular and fibrous (variable %)
For example both globular proteins myoglobin and hemoglobin are mainly composed of alpha helix (80%) however chymotrypsin (proteolytic enzyme) is completely devoid of alpha helix.
Moreover some fibrous proteins have high content of alpha helix such as myosin and fibrinogen.
Here we are dealing with short range intramolecular H-bonding interactions between peptide bond n and n+4 (first C=O second N-H ).
spiral structure made of 12 residues to >40
This will cause the backbone of the polypeptide to twist , around imaginary axis , by an equal amount forming a coil . Assuming spiral stair case shape.
Each alpha helix has approximate 3.6 residues per turn, with H-bonded peptide bonds directed parallel to the imaginary axis while the R groups of the side chain are perpendicular to the outside surface avoiding hindrance or interference.
Extensive tightly packed H-bonding in the inner core stabilizes the alpha helix.
Some alpha helixes have both hydrophobic and hydrophilic sides (amphipathic )
Destabilizing factors of alpha helix:
We have to consider the () core versus the () surface.
Inner core: () between peptide bonds.
Outer core is stabilized / destabilized by() interactions or the () with the () .
If a polypeptide has many Glu residues for example, it thus has a net () charge, so they will be () force that will destabilize the () surface.
On the other hand having () (positively charged) and () (negatively charged) () are favorable provided they do not force or push the H bond in the inner core, below the permissible () (the distance at which the () force is maximal and () force is minimal). Hence it is important to maintain the balance between outer and inner force s in protein conformation.
In addition the presence of adjacent, () groups (2 examples () ) () alpha helical structure. The most disruptive of alpha helical structure is the aa () .
The N is () amine so when it forms a peptide bond there is no () to get involved in () ; disrupting the net work in the () core. So in proteins where there is proline you would expect a () to occur.
Does this mean that proteins with proline residue cannot form helixes? The best answer is () an () protein, () component of () tissue, bone () .. Etc. it has distinctive aa composite: () , () and (). It folds as a () distorted alpha helices.
Destabilizing factors of alpha helix:
We have to consider the inner core versus the outer surface.
Inner core: H-bonding between peptide bonds.
Outer core is stabilized / destabilized by R-R interactions or the R-group with the environment .
If a polypeptide has many Glu residues for example, it thus has a net negative charge, so they will be repulsive force that will destabilize the outer surface.
On the other hand having lysine (positively charged) and glutamate (negatively charged) electrostatic forces are favorable provided they do not force or push the H bond in the inner core, below the permissible Vander Vals radii (the distance at which the attractive force is maximal and repulsive force is minimal). Hence it is important to maintain the balance between outer and inner force s in protein conformation.
In addition the presence of adjacent, bulky groups (2 examples (phe and trp) alpha helical structure. The most disruptive of alpha helical structure is the aa proline .
The N is secondary amine so when it forms a peptide bond there is no free H to get involved in H-bonding ; disrupting the net work in the inner core. So in proteins where there is proline you would expect a bend to occur.
Does this mean that proteins with proline residue cannot form helixes? The best answer is collagen an extracellular protein, insoluble component of connective tissue, bone cartilage .. Etc. it has distinctive aa composite: proline , hydroxy proline and glycine. It folds as a triple distorted alpha helices.
Beta pleated sheet structures are characterized by a more extended structure characteristic of polypeptides with repetitive sequences and aa small side chain + () shape.
It involves interactions between peptides bonds involving both mainly () and possibly () molecular H-bonding.
Unlike the alpha helix between n and n+4 here we are dealing with longer stretch of aa (() residues folded / stacked in layers where then the peptide bonds interact via H-bond.
There are 2 types of beta pleated sheets in which the polypeptides run () to each other and () .
Parallel beta sheets has H-bonding that are distorted so they are less () than antiparallel, whereas in the antiparallel the H-bonds are () , better filling of space and more () . Typical example of antiparallel beta pleated sheets is () .
it is made up of () repeats : () . Because of its small size () is characteristic of beta sheets folded proteins because it can fit easily between the ().
Another type is () which are common in () proteins. Located at () of the protein composed of () affecting a change in direction of the polypeptide. They often contain () and () .
() usually occurs at position and () linked together by () forming a () .
Beta pleated sheet structures are characterized by a more extended structure characteristic of polypeptides with repetitive sequences and aa small side chain + zigzag shape.
It involves interactions between peptides bonds involving both mainly inter and possibly intra molecular H-bonding.
Unlike the alpha helix between n and n+4 here we are dealing with longer stretch of aa (10-15 residues folded / stacked in layers where then the peptide bonds interact via H-bond.
There are 2 types of beta pleated sheets in which the polypeptides run parallel to each other and antiparallel.
Parallel beta sheets has H-bonding that are distorted so they are less stable than antiparallel, whereas in the antiparallel the H-bonds are collinear , better filling of space and more stable . Typical example of antiparallel beta pleated sheets is silk protein .
it is made up of 6 repeats : gly-ser-gly-ala-gly-ala. Because of its small size gly is characteristic of beta sheets folded proteins because it can fit easily between the layers.
Another type is beta turns which are common in globular proteins. Located at surface of the protein composed of 4 amino acids affecting a change in direction of the polypeptide. They often contain glycine and proline .
glycine usually occurs at position and 4 linked together by H-bonding forming a loop .
PROTEIN KERATIN:
It is mainly alpha helical structure when the hair is exposed to () and () it changes, H-bonds in keratin are disrupted assuming a new secondary structure parallel beta pleated sheets.
The fact that the H- bonds in parallel beta pleated sheets are distorted, makes them () . Thus when the hair () it goes back to the native structure.
PROTEIN KERATIN:
It is mainly alpha helical structure when the hair is exposed to moist and heat it changes, H-bonds in keratin are disrupted assuming a new secondary structure parallel beta pleated sheets.
The fact that the H- bonds in parallel beta pleated sheets are distorted, makes them unstable. Thus when the hair dries it goes back to the native structure.
A transition between secondary and tertiary structure is called: ()
Combination of various secondary structures generates () ; for instance several alpha helices or beta pleated sheet –alpha helix –beta pleated sheets .
SSS are usually associated with a particular functional property such as binding of () () or ().
Examples include() and () found in () factors, mediating the binding of proteins to (). Therefore, these structural motifs help proteins attach to and interact with specific DNA sequences.
Combination of motifs generates a () forming for example a () like structure where you have beta pleated sheets surrounded by (). () are part of polypeptide that can independently fold leading to a () structure.
A transition between secondary and tertiary structure is called: super secondary structure
Combination of various secondary structures generates motifs ; for instance several alpha helices or beta pleated sheet –alpha helix –beta pleated sheets .
SSS are usually associated with a particular functional property such as binding of NAD ATP or small ion molecules
Examples include leucine zippers and zinc fingers found in transcription factors, mediating the binding of proteins to DNA. Therefore, these structural motifs help proteins attach to and interact with specific DNA sequences.
Combination of motifs generates a domain for example a barrel like structure where you have beta pleated sheets surrounded by alpha helices. domains are part of polypeptide that can independently fold leading to a tertiary structure.
Tertiary structures:
() or folding that produces a 3-d rigid structure in space.
() folding where different segments of the folded polypeptide, which are apart from each other in primary structure, are folded here in close proximity.
The final tertiary structure is an assembly of folded domain(s). So groups distant from each other come close to each other.
Hence as protein folds forming motifs, then several motifs into domains these domains will fold together involving side group interactions leading to a tertiary structure (3 dimensional structure in space).
A tertiary structure of a protein may be composed of () domain or () domains (collectively called tertiary structure).
Each domain has a characteristic () with () interior and () exterior.
() proteins composed of different domains can perform different tasks.
Tertiary structures:
supercoiling or folding that produces a 3-d rigid structure in space.
distant folding where different segments of the folded polypeptide, which are apart from each other in primary structure, are folded here in close proximity.
The final tertiary structure is an assembly of folded domain(s). So groups distant from each other come close to each other.
Hence as protein folds forming motifs, then several motifs into domains these domains will fold together involving side group interactions leading to a tertiary structure (3 dimensional structure in space).
A tertiary structure of a protein may be composed of single domain or several domains (collectively called tertiary structure).
Each domain has a characteristic geometry with hydrophobic interior and hydrophilic exterior.
multifunctional proteins composed of different domains can perform different tasks.
examples of tertiary structures:
HK: () is a () () () that catalyzes the () of () into () The enzyme has a () binding site at a cleft between () () . When it binds, the () () () move to close over the substrate trapping it for () to occur.
LDH: or () catalyzes () () of () into (). Each subunits is made of () domains one that () and the other that binds the substrate (() .
The FAS or () is composed of() domains . Domains() catalyze () while domain () catalyzes () reaction.
examples of tertiary structures:
HK: hexokinase is a single polypeptide enzyme that catalyzes the phosphorylation of glucose into glucose-6-phosphate. The enzyme has a glucose binding site at a cleft between surrounding domains . When it binds, the 2 surrounding domains move to close over the substrate trapping it for phosphorylation to occur.
LDH: or lactate dehydrogenase catalyzes reversible reduction of pyruvate into lactate. Each subunits is made of 2 domains one that NAD and the other that binds the substrate pyruvate .
The FAS or Fatty acid synthase is composed of 3 (I,II,III) domains . Domains I and II catalyze 6 enzymatic reactions while domain III catalyzes one reaction.
