Protein structure: Primary, secondary, tertiary & quatrenary (article) | Khan Academy
Read and learn for free about the following article: Chemistry of amino acids and in the formation of a new bond—a peptide bond between the two amino acids. The sequence of amino acids determines the basic structure of the protein. Biosci Biotechnol Biochem. Oct;57(10) Relationship between amino acid sequence and secondary structures of proteins in plants and cereals. Download Citation on ResearchGate | Relationship between Amino Acids Sequences and Protein Structures: Folding Patterns and Sequence Patterns | Two.
Protein Structure: Primary, Secondary, Tertiary, Quatemary Structures
Hence, some amino acid sequences do not uniquely determine secondary structure. Tertiary interactions—interactions between residues that are far apart in the sequence—may be decisive in specifying the secondary structure of some segments. The context is often crucial in determining the conformational outcome.
The conformation of a protein evolved to work in a particular environment or context. Many sequences can adopt alternative conformations in different proteins. Pathological conditions can result if a protein assumes an inappropriate conformation for the context. Striking examples are prion diseases, such as Creutzfeldt-Jacob disease, kuru, and mad cow disease. These conditions result when a brain protein called a prion converts from its normal conformation designated PrP C to an altered one PrPSc.
This conversion is self-propagating, leading to large aggregates of PrPSc. The role of these aggregates in the generation of the pathological conditions is not yet understood. Protein Folding Is a Highly Cooperative Process As stated earlier, proteins can be denatured by heat or by chemical denaturants such as urea or guanidium chloride.
For many proteins, a comparison of the degree of unfolding as the concentration of denaturant increases has revealed a relatively sharp transition from the folded, or native, form to the unfolded, or denatured, form, suggesting that only these two conformational states are present to any significant extent Figure 3. A similar sharp transition is observed if one starts with unfolded proteins and removes the denaturants, allowing the proteins to fold. Most proteins show a sharp transition from the folded to unfolded form on treatment with increasing concentrations of denaturants.
For example, suppose that a protein is placed in conditions under which some part of the protein structure is thermodynamically unstable. As this part of the folded structure is disrupted, the interactions between it and the remainder of the protein will be lost. The loss of these interactions, in turn, will destabilize the remainder of the structure. Thus, conditions that lead to the disruption of any part of a protein structure are likely to unravel the protein completely. The structural properties of proteins provide a clear rationale for the cooperative transition.
The consequences of cooperative folding can be illustrated by considering the contents of a protein solution under conditions corresponding to the middle of the transition between the folded and unfolded forms.
Structures that are partly intact and partly disrupted are not thermodynamically stable and exist only transiently.
Cooperative folding ensures that partly folded structures that might interfere with processes within cells do not accumulate. Components of a Partially Denatured Protein Solution.
In a half-unfolded protein solution, half the molecules are fully folded and half are fully unfolded. Proteins Fold by Progressive Stabilization of Intermediates Rather Than by Random Search The cooperative folding of proteins is a thermodynamic property; its occurrence reveals nothing about the kinetics and mechanism of protein folding. How does a protein make the transition from a diverse ensemble of unfolded structures into a unique conformation in the native form?
One possibility a priori would be that all possible conformations are tried out to find the energetically most favorable one. How long would such a random search take? Consider a small protein with residues. Clearly, it would take much too long for even a small protein to fold properly by randomly trying out all possible conformations.
The enormous difference between calculated and actual folding times is called Levinthal's paradox. The way out of this dilemma is to recognize the power of cumulative selection. An astronomically large number of keystrokes, of the order ofwould be required.
However, suppose that we preserved each correct character and allowed the monkey to retype only the wrong ones. In this case, only a few thousand keystrokes, on average, would be needed. The crucial difference between these cases is that the first employs a completely random search, whereas, in the second, partly correct intermediates are retained. A monkey randomly poking a typewriter could write a line from Shakespeare's Hamlet, provided that correct keystrokes were retained.
In the two computer simulations shown, the cumulative number of keystrokes is given at the left more The essence of protein folding is the retention of partly correct intermediates. However, the protein-folding problem is much more difficult than the one presented to our simian Shakespeare.
First, the criterion of correctness is not a residue-by-residue scrutiny of conformation by an omniscient observer but rather the total free energy of the transient species. Proline is typically found in bends, unstructured regions between secondary structures. Tertiary structure The overall three-dimensional structure of a polypeptide is called its tertiary structure.
The tertiary structure is primarily due to interactions between the R groups of the amino acids that make up the protein. R group interactions that contribute to tertiary structure include hydrogen bonding, ionic bonding, dipole-dipole interactions, and London dispersion forces — basically, the whole gamut of non-covalent bonds. For example, R groups with like charges repel one another, while those with opposite charges can form an ionic bond.
Similarly, polar R groups can form hydrogen bonds and other dipole-dipole interactions. Also important to tertiary structure are hydrophobic interactions, in which amino acids with nonpolar, hydrophobic R groups cluster together on the inside of the protein, leaving hydrophilic amino acids on the outside to interact with surrounding water molecules.
Disulfide bonds, covalent linkages between the sulfur-containing side chains of cysteines, are much stronger than the other types of bonds that contribute to tertiary structure. They act like molecular "safety pins," keeping parts of the polypeptide firmly attached to one another. Image of a hypothetical polypeptide chain, depicting different types of side chain interactions that can contribute to tertiary structure.
These include hydrophobic interactions, ionic bonds, hydrogen bonds, and disulfide bridge formation. However, some proteins are made up of multiple polypeptide chains, also known as subunits. When these subunits come together, they give the protein its quaternary structure. In general, the same types of interactions that contribute to tertiary structure mostly weak interactions, such as hydrogen bonding and London dispersion forces also hold the subunits together to give quaternary structure.
Flowchart depicting the four orders of protein structure. Denaturation and protein folding Each protein has its own unique shape.
If the temperature or pH of a protein's environment is changed, or if it is exposed to chemicals, these interactions may be disrupted, causing the protein to lose its three-dimensional structure and turn back into an unstructured string of amino acids.
When a protein loses its higher-order structure, but not its primary sequence, it is said to be denatured. Denatured proteins are usually non-functional.
Chemistry of amino acids and protein structure
For some proteins, denaturation can be reversed. Other times, however, denaturation is permanent. One example of irreversible protein denaturation is when an egg is fried.
The albumin protein in the liquid egg white becomes opaque and solid as it is denatured by the heat of the stove, and will not return to its original, raw-egg state even when cooled down. Researchers have found that some proteins can re-fold after denaturation even when they are alone in a test tube. The hydrogen bonds make this structure especially stable.
The side-chain substituents of the amino acids fit in beside the N-H groups. The sheet conformation consists of pairs of strands lying side-by-side. The carbonyl oxygens in one strand hydrogen bond with the amino hydrogens of the adjacent strand.
The two strands can be either parallel or anti-parallel depending on whether the strand directions N-terminus to C-terminus are the same or opposite. Tertiary Structure The overall three-dimensional shape of an entire protein molecule is the tertiary structure.
The protein molecule will bend and twist in such a way as to achieve maximum stability or lowest energy state. Although the three-dimensional shape of a protein may seem irregular and random, it is fashioned by many stabilizing forces due to bonding interactions between the side-chain groups of the amino acids. Under physiologic conditions, the hydrophobic side-chains of neutral, non-polar amino acids such as phenylalanine or isoleucine tend to be buried on the interior of the protein molecule thereby shielding them from the aqueous medium.
The alkyl groups of alanine, valine, leucine and isoleucine often form hydrophobic interactions between one-another, while aromatic groups such as those of phenylalanine and tryosine often stack together. Acidic or basic amino acid side-chains will generally be exposed on the surface of the protein as they are hydrophilic. The formation of disulfide bridges by oxidation of the sulfhydryl groups on cysteine is an important aspect of the stabilization of protein tertiary structure, allowing different parts of the protein chain to be held together covalently.
Additionally, hydrogen bonds may form between different side-chain groups. As with disulfide bridges, these hydrogen bonds can bring together two parts of a chain that are some distance away in terms of sequence. Salt bridges, ionic interactions between positively and negatively charged sites on amino acid side chains, also help to stabilize the tertiary structure of a protein. Quaternary Structure Many proteins are made up of multiple polypeptide chains, often referred to as protein subunits.
These subunits may be the same as in a homodimer or different as in a heterodimer. The quaternary structure refers to how these protein subunits interact with each other and arrange themselves to form a larger aggregate protein complex. The final shape of the protein complex is once again stabilized by various interactions, including hydrogen-bonding, disulfide-bridges and salt bridges.
The four levels of protein structure are shown in Figure 2. Protein Stability Due to the nature of the weak interactions controlling the three-dimensional structure, proteins are very sensitive molecules. The term native state is used to describe the protein in its most stable natural conformation in situ.
This native state can be disrupted by a number of external stress factors including temperature, pH, removal of water, presence of hydrophobic surfaces, presence of metal ions and high shear. The loss of secondary, tertiary or quaternary structure due to exposure to a stress factor is called denaturation.
Denaturation results in unfolding of the protein into a random or misfolded shape.