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Margaret Oakley Dayhoff originated the idea of protein superfamilies after noticing that proteins with diverse amino acid sequences can have similar tertiary structures. Why can protein structure be more highly conserved than individual amino acid sequences?

Short Answer

Expert verified
Protein structure is highly conserved due to its critical role in function, despite variations in amino acid sequences.

Step by step solution

01

Understand Protein Structure

Proteins are made up of chains of amino acids that fold into complex three-dimensional shapes. The function of a protein is largely determined by its three-dimensional structure, which is established by the specific folding pattern of its amino acid chain.
02

Recognize the Importance of Structure

The three-dimensional structure of proteins is crucial because it determines how proteins interact with other molecules and perform their functions. Even if the amino acid sequence varies, the structure can remain functional if the key structural features are preserved.
03

Identify Conservative Substitutions

Proteins can undergo conservative amino acid substitutions, where one amino acid is replaced by another with similar properties. This alteration may not significantly affect the protein's folding and thus its structure. As a result, the protein retains its function despite changes in its amino acid sequence.
04

Understand Evolutionary Pressure

Evolution tends to preserve structures that are essential for the protein's function. As a consequence, the tertiary structure of proteins is often more conserved than their amino acid sequences because maintaining the structure is crucial for survival and proper biological function.
05

Explain the Role of Superfamilies

Protein superfamilies are classified based on their structural similarities rather than amino acid sequences. This reflects the idea that proteins can have similar structures and functions even if their sequences differ, highlighting the conservation of protein structure over sequence.

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Key Concepts

These are the key concepts you need to understand to accurately answer the question.

Protein Superfamilies
Protein superfamilies are groups of proteins that share similar structures even if their amino acid sequences are vastly different. Margaret Oakley Dayhoff was a visionary in recognizing this concept, seeing that structural conservation often crosses the boundaries of sequence variations.
Proteins are assessed based on their structural characteristics, allowing scientists to classify them in superfamilies. This classification system is instrumental in understanding how proteins evolve and interact within the human body.
Protein superfamilies serve as a fascinating example of nature’s ability to maintain function despite genetic variation. When proteins are part of the same superfamily, they often perform the same function in different organisms, illustrating the adaptability and resourcefulness of biological systems. By focusing on superfamilies, researchers can better predict protein function and develop new tools in biotechnology and medicine.
Amino Acid Sequence
The amino acid sequence of a protein is essentially its blueprint. This sequence is a linear chain of amino acids that will fold into a unique three-dimensional shape after being assembled. Each protein’s function is deeply tied to its specific shape, which is dictated by the order of its amino acids.
However, while the amino acid sequence is the script, the story told can sometimes differ slightly without losing its essence. This happens through what's known as conservative substitutions, where changes in the sequence do not significantly alter the protein’s shape or function. These substitutions can vary slightly, maintaining the integrity of the protein’s activity.
Although it is common to think of protein similarities in terms of sequences, the ability to tolerate sequence changes while preserving function highlights the complex and flexible nature of proteins. This flexibility is due to the resilient nature of protein structures that can often adapt to slight variations in the sequence without losing their functional role.
Tertiary Structure
The tertiary structure of a protein is its ultimate three-dimensional form, a shape that is critical to its function. This structure results from the complete folding of a protein's amino acid chain, influenced by interactions such as hydrogen bonds, ionic interactions, and hydrophobic packing.
The importance of tertiary structure cannot be overstated; it acts as the framework for the protein’s activity. Even when the amino acid sequence changes through mutations or variations, the tertiary structure can remain stable as long as key structural determinants endure.
Protein’s flexibility and robustness come into play here. They allow for a variety of amino acid configurations that may not disrupt the final tertiary form. This stability is crucial for biological functionality, enabling proteins to carry out their roles effectively in cellular processes.
The stability of the tertiary structure amid sequence alterations is a major reason why protein structures tend to be conserved across species, despite significant differences in their genetic codes.
Evolutionary Biology
In evolutionary biology, the conservation of protein structures over sequences is a testament to the pressures of natural selection. Evolution seeks to retain those structures that are vital for survival and successful biological functions.
The environments in which organisms evolve select for those protein folds and configurations that continue to be effective and efficient. Over time, even though the sequences might undergo mutations, the structures that are essential for life remain mostly unchanged.
This is why the tertiary structure is more conserved than the amino acid sequences, directly impacting an organism's adaptability and longevity. Evolutionary biology underscores the importance of studying protein structures; it helps scientists to understand the evolutionary lineage of organisms and to predict the functionality of unknown proteins.
In summary, nature equips proteins with the remarkable ability to maintain their roles, ensuring that life continues smoothly despite inevitable genetic variations and challenges.

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Most popular questions from this chapter

Properties of the Peptide Bond In x-ray studies of crystalline peptides, Linus Pauling and Robert Corey found that the \(\mathrm{C}-\mathrm{N}\) bond in the peptide link is intermediate in length (1.32 Å) between a typical \(\mathrm{C}-\mathrm{N}\) single bond \(\left(1.49 \AA^{\circ}\right)\) and \(\mathrm{a} \mathrm{C}=\mathrm{N}\) double bond \((1.27\) A). They also found that the peptide bond is planar (all four atoms attached to the C-N group are located in the same plane) and that the two \(a\)-carbon atoms attached to the \(\mathrm{C}-\mathrm{N}\) are always trans to each other (on opposite sides of the peptide bond). a. What does the length of the \(\mathrm{C}-\mathrm{N}\) bond in the peptide linkage indicate about its strength and its bond order (i.e., whether it is single, double, or triple)? b. What do Pauling and Corey's observations tell us about the ease of rotation about the \(\mathrm{C}-\mathrm{N}\) peptide bond?

Mirror-Image Proteins As noted in \(\underline{\text { Chapter } 3}\), "The amino acid residues in protein molecules are almost all L stereoisomers." It is not clear whether this selectivity is necessary for proper protein function or is an accident of evolution. To explore this question, Milton and colleagues (1992) published a study of an enzyme made entirely of \(\mathrm{D}\) stereoisomers. The enzyme they chose was HIV protease, a proteolytic enzyme made by HIV that converts inactive viral preproteins to their active forms. Previously, Wlodawer and coworkers (1989) had reported the complete chemical synthesis of HIV protease from L-amino acids (the L-enzyme), using the process shown in Eigure 3-30. Normal HIV protease contains two Cys residues, at positions 67 and \(95 .\) Because chemical synthesis of proteins containing Cys is technically difficult, Wlodawer and colleagues substituted the synthetic amino acid L- \(a\)-amino- \(n\)-butyric acid (Aba) for the two Cys residues in the protein. In the authors' words, this was done to "reduce synthetic difficulties associated with Cys deprotection and ease product handling." a. The structure of Aba is shown below. Why was this a suitable substitution for a Cys residue? Under what circumstances would it not be suitable?

Which structural biology method (CD, x-ray crystallography, NMR, or cryo-EM) is best suited to each task? a. Obtaining an ultra-high resolution \((<1.5 \AA)\) structure of a drug bound to its protein target b. Obtaining a low-to-medium resolution (5-10 \AA) reconstruction of the \(11 \mathrm{MDa}(11,000,000 \mathrm{Da})\) bacterial flagellar motor c. Identifying the protonation state and \(\mathrm{p} K_{\mathrm{a}}\). of a His side chain in an enzyme active site d. Determining whether a protein is intrinsically disordered or contains secondary structure elements

Under the proper environmental conditions, the salt-loving archaeon Halobacterium halobium synthesizes a membrane protein \(\left(M_{\mathrm{r}} 26,000\right)\), known as bacteriorhodopsin, which is purple because it contains retinal (see Fig, 10-20). Molecules of this protein aggregate into "purple patches" in the cell membrane. Bacteriorhodopsin acts as a light- activated proton pump that provides energy for cell functions. X-ray analysis of this protein reveals that it consists of seven parallel \(a\)-helical segments, each of which traverses the bacterial cell membrane (thickness \(45 \AA\) ). Calculate the minimum number of amino acid residues necessary for one segment of \(a\) helix to traverse the membrane completely. Estimate the fraction of the bacteriorhodopsin protein that is involved in membrane-spanning helices. (Use an average amino acid residue weight of 110 .)

Some natural proteins are rich in disulfide bonds, and their mechanical properties, such as tensile strength, viscosity, and hardness, correlate with the degree of disulfide bonding. a. Glutenin, a wheat protein rich in disulfide bonds, imparts the cohesive and elastic character of dough made from wheat flour. Similarly, the hard, tough nature of tortoise shell results from the extensive disulfide bonding in its \(a\) keratin. What is the molecular basis for the correlation between disulfide-bond content and mechanical properties of the protein? b. Most globular proteins denature and lose their activity when they are briefly heated to \(65^{\circ} \mathrm{C}\). However, the denaturation of globular proteins that contain multiple disulfide bonds often requires longer heat exposure at higher temperatures. One such protein is bovine pancreatic trypsin inhibitor (BPTI), which has 58 amino acid residues in a single peptide chain and contains three disulfide bonds. After a solution of denatured BPTI is cooled, the protein regains its activity. What is the molecular basis for this property of BPTI?

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