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Hidden structures in cells: How do conjugated helices drive biological functions?
In the operation of life, the interaction between molecules is the cornerstone of the function of organisms. Among them, the conjugated coil is a striking structural motif that exists in approximately 5-10% of proteins. This structure consists of 2 to 7 alpha helices wrapped together, like a rope. These helices not only provide stability, but also play a vital role in regulating gene expression and other biological functions.
The conjugated helical motif enables many proteins to interact with each other and form complex cellular structures.
Discovery of the conjugated helix
The concept of conjugated helix was first proposed independently by Linus Pauling and Francis Crick. In the summer of 1952, Pauling visited Crick's laboratory. The two scientists discussed many topics, and Crick suddenly asked Pauling if he had ever considered the term "conjugated helix". Paulin said he had thought about it, and this conversation led Paulin to continue to study the topic in depth after returning to the United States and submit a long paper to the journal Nature.
Crick's paper, although shorter, came before Pauling's, sparking a controversy in the scientific community.
After many communications and debates, Crick's laboratory finally confirmed that the idea was independently reached by the two scientists and no intellectual property theft occurred. Crick's contribution was to propose the concept of "conjugated helix" and provide a mathematical method to determine its structure.
Molecular structure
The conjugated helix is usually composed of a repeating pattern (hxxhcxc) of hydrophobic (h) and charged (c) amino acid residues, known as a heptad repeat. Within this repeat, positions are labeled abcdefg, where a and d are hydrogen hydrophobic positions, typically occupied by isoleucine, leucine, or valine. When a sequence has this repeating pattern and folds into an alpha-helical secondary structure, the hydrogen hydrophobic residues appear as a ‘strip’ winding around the helix, forming an amphipathic structure.
The interactions between the conjugated helices provide the thermodynamic driving force for the formation of polymers.
Biological effects
Conjugated helices are primarily used to promote interactions between proteins, helping proteins or domains lock into each other. This property is crucial for a variety of biological functions, including membrane fusion, molecular spacing, and functions related to vesicle motility.
Membrane fusion
The conjugated helical domain plays an important role in HIV infection. When the virus enters a CD4-positive cell, the glycoprotein gp120 binds to the CD4 receptor and the core receptor. At this point, gp120 and gp41 form a ternary complex and ultimately guide the fusion of the virus and cell membrane through a conjugation mechanism. The N-terminal fusion peptide sequence of gp41 is fixed in the host cell to achieve fusion. Recently, inhibitors based on the HR2 region, Fuzeon, have been developed to counteract this process, aiming to reduce HIV's ability to infect.
As molecular spacer
The conjugated helical motif can also serve as separators between objects within cells. The length of these molecular spacers, conjugated helical domains, is conserved, and crucially they prevent interactions between protein domains. For example, Omp-α protein is a typical example, which maintains the distance between components through conjugated helices.
Design and Application
Conjugated helices offer a design solution to the protein folding problem. Through the study of the conjugated helix of GCN4, scientists established a grammar that can effectively predict the oligomeric state based on the amino acid sequence. This makes it possible to use conjugated helices in the synthesis of nanostructures, thereby promoting the development of new drug delivery systems.
Using the functionality of conjugated helices, scientists are developing more precise drug delivery mechanisms to improve therapeutic efficiency.
With the in-depth study of the conjugated helix structure, its application potential in fields such as medicine, bioengineering and nanotechnology will undoubtedly continue to expand in the future. How can we use this mysterious structure to reshape our understanding of how life works?
