Question

Traditionally, gene sequence homology implied functional similarity. Even though two proteins may contain over 60 percent sequence identity, only about 38 percent have identical functions (Roy et al., 2008 ). In some cases, closely related homologs may engender completely different classes of proteins (enzymes). Consider the 3 D structure of two proteins with 60 percent homology with entirely different functions. Explain how different functions may evolve by discussing the position of the homologous amino acid track, its relation to nonhomologous tracks, and the role that chaperones (Chapter 14 ) may play in determining protein function.

Short answer

Answer: Two proteins with 60 percent homology can have entirely different functions due to the position of the homologous amino acid track, the effect of nonhomologous tracks on protein structure, and the role of chaperones in protein folding. These factors can influence the 3D structure and the binding capabilities of the proteins, ultimately leading to distinct functions, even in structurally related proteins.

Step-by-step solution

Understand the terms

It is essential to understand what gene sequence homology, sequence identity, amino acid tracks, and chaperones are. Homology refers to the similarity between genes or proteins in different species arising from a common ancestor. Sequence identity is the number of amino acids that are identical between two aligned sequences, divided by their length. Amino acid tracks are continuous stretches of amino acids within the primary sequence of a protein. Chaperones are proteins that assist in the folding of other proteins.

Discuss the position of the homologous amino acid track

While two proteins may share a high percentage of homology, that does not necessarily mean their functions are identical. The position of the homologous amino acid track in each protein can determine how it interacts with other parts of the protein or with other molecules, influencing its function. If the homologous tracks are situated differently within the 3D structure of the proteins, it can lead to variation in their functions.

Consider the role of nonhomologous tracks

Differences in the protein's function can also arise from nonhomologous amino acid tracks present in the proteins. Nonhomologous tracks may affect the overall structure and folding of the protein, which in turn influences its function. If the nonhomologous tracks interact differently with the homologous tracks, they can lead to significant differences in the protein's activity or binding capabilities, resulting in distinct functions.

Discuss the role of chaperones in determining protein function

Chaperones are responsible for assisting in the proper folding of proteins. The way a protein folds is essential for its function, as it determines the position of amino acids in the 3D structure, enabling specific interactions with other molecules. Chaperones may recognize and interact with different amino acid sequences in homologous proteins, which can lead to different folding patterns. Consequently, the role of chaperones in protein folding can be significant in determining the ultimate function of a protein.

Conclusion

In conclusion, different functions may evolve in proteins with high sequence homology due to the position of the homologous amino acid track, the effect of nonhomologous tracks on protein structure, and the role of chaperones in protein folding. These factors can influence the 3D structure and the binding capabilities of the proteins, ultimately leading to distinct functions, even in structurally related proteins.

Key concepts

Protein Function Evolution

The evolution of protein function is a fascinating aspect of molecular biology that explains how proteins with similar gene sequences may end up with entirely different functionalities. Despite a high degree of sequence homology, which suggests a common ancestor, the definitive function of a protein is shaped by more than just genetic similarity.

In the realm of proteins, subtle changes can have major impacts. Small shifts in key amino acids - often caused by mutations over time - can alter the way a protein interacts with other molecules or performs its role in the cell. These microscopic variations in the amino acid sequence are like a butterfly effect in protein evolution; a single change can reshape the entire functional landscape of a protein.

Moreover, natural selection plays a crucial role in protein function evolution. Proteins that develop advantageous traits are more likely to be passed down through generations. Over time, this selective process contributes to the diversification of protein functions, even among proteins that started off nearly identical in structure and sequence.

Amino Acid Tracks

Deconstructing the concept of amino acid tracks, it's essential to consider them as the 'phrases' within the language of proteins that can substantially affect a protein's structure and function. These tracks are sequences of amino acids that exhibit a continuous stretch within a protein's primary structure and can act much like the keystone in an arch; they maintain the integrity of the overall shape.

The positioning of these amino acid tracks within a protein can greatly influence how it folds and how it interfaces with other proteins or molecules. When these tracks are homologous, they might suggest a similar function at first glance. However, their impact on the protein's function is far more nuanced. The nuanced role of these tracks extends to their involvement in the stabilization of protein structure, the specificity of binding sites, and influencing the overall folding pattern, which, in turn, can lead to a diversified functionality even within proteins sharing high sequence homology.

Protein Folding

Protein folding is a delicate and intricate process that transforms a linear sequence of amino acids into a three-dimensional functional machine. This intricate process is crucial because a protein's function is intrinsically linked to its shape. Misfolded proteins can result in loss of function or, worse, the development of diseases.

Folding Pathways and Energy Landscapes

Protein folding is directed by the sequence itself, guiding the protein along a folding pathway towards the lowest energy state, known as the native conformation. Imagine a hiker finding the most efficient route down a mountain; similarly, proteins 'seek' the most stable configuration amidst an array of possible structures.

Remarkably, the folding process is aided by the interactions among amino acids, whether they're part of homologous tracks or regions of difference within the protein. This intricate dance of chemical bonds and interactions determines the precise structure that the protein will ultimately assume, laying the foundation for its specific role within the cell.

Molecular Chaperones

Molecular chaperones are the unsung heroes in the world of protein folding; they're the molecules that ensure proteins reach their functional form. Chaperones do not impart a final structure upon proteins but rather facilitate the journey, preventing incorrect interactions that could lead to dysfunctional or aggregated proteins.

Think of these chaperones as seasoned guides, preventing proteins from making wrong turns as they navigate the complex folding pathway. Just as a guide might recognize a traveler by their attire, chaperones are attuned to specific amino acid sequences and their folding status. They jump into action, assisting where necessary to avoid molecular mishaps.

Guardians Against Stress

Chaperones also play a critical role under stress conditions, where they work tirelessly to refold damaged proteins or to help in the degradation process if refolding is not an option. By doing so, they maintain cellular health and are essential in managing the misfolding that can be detrimental to the cell's wellbeing. The nuanced roles of these molecular chaperones extend beyond mere assistance in folding; they can dictate the fate of a protein and hence are integral to the functional diversity arising from proteins with similar sequence homology.