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From antiviral to cell division: What are the surprising roles of conjugated helices in biology?
Conjugated helix is a structural feature in proteins, consisting of 2-7 alpha helices rolled together like a rope. This structure is found in approximately 5-10% of proteins and has a variety of functions. As one of the most extensive details of protein-protein interactions, conjugated helices play an indispensable role in biological research.
Discovery process
The concept of conjugated helix once caused controversy in the study of α-keratin. Linus Pauling and Francis Crick reached this conclusion independently and at almost the same time. In the summer of 1952, Paulin visited Crick's laboratory in England, and the two exchanged views on various topics. When Crick asked Pauling if he had ever considered conjugated helices, Pauling said he had. Paulin then continued his research in this area after returning to the United States and submitted a long manuscript to Nature magazine in October.
"Studies of conjugated helices reveal a deep connection between protein structure and its function."
Crick believed Paulin had plagiarized his ideas and submitted a shorter article to Nature a few days later. Eventually, after repeated correspondence and controversy, Crick's laboratory announced that both parties had reached the conclusion independently and that no intellectual theft had occurred.
Molecular structure
Conjugated helices typically contain a repeating pattern - hxxhcxc, which is a repeat of hydrophobic (h) and charged (c) amino acid residues, known as a heptad repeat. In the heptad repeat sequence, the a and d positions are usually occupied by hydrophobic amino acids such as isoleucine, leucine or valine. These repeating sequences are folded into an alpha-helical structure, where the hydrophobic residues from the intertwined alpha-helices appear as a "stripe" and form an amphipathic structure.
"The tight packing of the conjugated helices provides a strong thermodynamic driving force."
Alpha helices can be arranged in parallel or antiparallel directions and usually take the form of a left-handed supercoil. Although uncommon, right-handed helices can be observed in small quantities in both natural and designed proteins.
Biological Roles
Because conjugated helical structures are found throughout many proteins, they help to perform various functions in the cell, with the main purpose of facilitating interactions between proteins and keeping them or their regions connected. Characterization of these functions includes membrane fusion, molecular spacing, oligomer labeling, vesicle motility, and cellular architecture, among others.
Membrane fusion
The conjugated helical domain plays an important role in HIV infection. When the three gp120 subunits bind to the CD4 receptor and the core receptor, the virus enters CD4-positive cells. gp120 and gp41 are associated with each other through van der Waals forces. Ultimately, the fusion peptide sequence at the N-terminus of gp41 is fixed to the host cell and, through a spring-and-clock mechanism, brings the virus and cell membranes sufficiently close to promote fusion.
As molecular spacer
The structure of the conjugated helix can also serve as a molecular spacer inside cells, and its length is highly conserved. The function of these spacers is to prevent unwanted interactions between protein regions or to mediate vesicle trafficking within the cell. For example, Omp-α in T. maritima is an example.
As oligomer marker
Due to their specific interactivity, conjugated helices can be used as "tags" to stabilize or enhance specific oligomeric states. The study showed that conjugated helical interactions drive the polymerization of the BBS2 and BBS7 subunits of the BBSome.
Biomedical Applications
As a building block with simple design and diverse functions, conjugated helices have been used in the development of many nanostructures in recent years. They have potential value in areas such as drug delivery, tissue regeneration, and protein folding.
"Conjugated helices can provide stability and specificity to drug delivery systems, enhancing therapeutic efficacy."
In addition, by utilizing the oligomeric capacity of conjugated helices, it is possible to increase antigen display in vaccines, thereby improving their effectiveness. However, continued exploration and research are still needed to overcome the challenges of stability.
From antiviral response strategies to the coordination of cell division processes, the importance of conjugated helices in life sciences cannot be ignored. In the future, the potential applications of this structure may help us unlock more mysteries of life. Are you ready to explore this endless possibility?
