Histatins: Peptides with a license to kill
(2024) KEMR30 20232Department of Chemistry
- Abstract
- Histatins are a family of human salivary peptides which act as a part of the innate immune system. There are three main members of the family: Histatin 1 (Hst1), Histatin 3 (Hst3), and Histatin 5 (Hst5). Histatins have long been known to possess differing antimicrobial properties, such as antifungal and antiviral capabilities. Hst5 is generally described as the most potent antifungal peptide in the Histatin family but, curiously, does not excel against viruses. Hst1, on the other hand, has been shown to possess significant antiviral capabilities, whereas Hst3 is both antiviral and antifungal. This project studies differences in the main Histatin members from a structural and behavioural perspective, using X-ray scattering (SAXS), Molecular... (More)
- Histatins are a family of human salivary peptides which act as a part of the innate immune system. There are three main members of the family: Histatin 1 (Hst1), Histatin 3 (Hst3), and Histatin 5 (Hst5). Histatins have long been known to possess differing antimicrobial properties, such as antifungal and antiviral capabilities. Hst5 is generally described as the most potent antifungal peptide in the Histatin family but, curiously, does not excel against viruses. Hst1, on the other hand, has been shown to possess significant antiviral capabilities, whereas Hst3 is both antiviral and antifungal. This project studies differences in the main Histatin members from a structural and behavioural perspective, using X-ray scattering (SAXS), Molecular Dynamics (MD) simulation, and Circular Dichroism (CD). Current SAXS data describe all three peptides as intrinsically disordered, with Hst1 and Hst3 showing signs of being partially ordered with salt dependency. MD simulations and CD data show a slight imprint of secondary structure elements with largely disordered behaviour. Based on SAXS, Hst1 could potentially self-associate, while Hst3 likely does not. Hst5 is known to refrain from self-associating. Hst3 and Hst5 share a lot of behavioural patterns but are not identical. Hst3, unlike Hst5, appears to expand in more concentrated environments based on the radius of gyration values derived from SAXS spectra. (Less)
- Popular Abstract
- It is a fact of the human condition that people suffer. One of the most despised sources of human suffering is sickness. From colds to cancer, illness has haunted humanity since its genesis. Luckily, our bodies have an immune system which has evolved to protect us from outside threats such as malicious bacteria and viruses. The immune system is an incredibly complicated web of differing cells and systems based on molecules and chemistry. Antibodies are a great example to visualise this since it is not an organism but a protein. Proteins are a group of biomolecules that perform numerous bodily tasks, from structuring up muscles to breaking down waste products. A protein consists of a chain, or multiple chains, which are built from amino... (More)
- It is a fact of the human condition that people suffer. One of the most despised sources of human suffering is sickness. From colds to cancer, illness has haunted humanity since its genesis. Luckily, our bodies have an immune system which has evolved to protect us from outside threats such as malicious bacteria and viruses. The immune system is an incredibly complicated web of differing cells and systems based on molecules and chemistry. Antibodies are a great example to visualise this since it is not an organism but a protein. Proteins are a group of biomolecules that perform numerous bodily tasks, from structuring up muscles to breaking down waste products. A protein consists of a chain, or multiple chains, which are built from amino acids. Amino acids are a chemical group which comes in different variations. Different combinations of amino acids will lead to different protein behaviours. One of the most defining behaviours of a protein is its fold. A fold is the stable 3D orientation that a protein takes on in the body. Not all proteins have a fold; however, a significant group called intrinsically disordered proteins (IDPs) cycles through a set of structures in so- lution. An example of such a protein is Histatin 5 (Hst5), a human saliva protein that is part of the innate immune system and the first line of defence against germs. Hst5 is an antifungal molecule which primarily fights fungi which cause oral infections. Other Histatins exist, mainly Histatin 1 (Hst1) and Histatin 3 (Hst 3). These are also saliva proteins but are not as effective in killing fungus as killing viruses, which Hst5 is not very potent against. This is notable since all three proteins have similar amino acid combinations. This report focuses on understanding why these peptides are different. Studying such variation is important because it allows better insight into our immune system and could lead to future medicinal development. This study uses various methods, such as Molecular Dynamics (MD) simulation and X-ray scattering (SAXS). MD is a computer-simulating technique which applies Newtonian physics to model atomic movements. SAXS is an experimental method of illuminating a protein sample with X-ray light. The light bounces off the sample in a predictable way, which can be used to unravel information about the protein. (Less)
Please use this url to cite or link to this publication:
http://lup.lub.lu.se/student-papers/record/9144931
- author
- Svensson, Oskar LU
- supervisor
-
- Marie Skepö LU
- organization
- course
- KEMR30 20232
- year
- 2024
- type
- H1 - Master's Degree (One Year)
- subject
- keywords
- Histatin, Hst5, Hst3, Hst1, SAXS, Molecular dynamics, Physical chemistry
- language
- English
- id
- 9144931
- date added to LUP
- 2024-01-17 11:29:37
- date last changed
- 2024-01-17 11:29:37
@misc{9144931,
abstract = {{Histatins are a family of human salivary peptides which act as a part of the innate immune system. There are three main members of the family: Histatin 1 (Hst1), Histatin 3 (Hst3), and Histatin 5 (Hst5). Histatins have long been known to possess differing antimicrobial properties, such as antifungal and antiviral capabilities. Hst5 is generally described as the most potent antifungal peptide in the Histatin family but, curiously, does not excel against viruses. Hst1, on the other hand, has been shown to possess significant antiviral capabilities, whereas Hst3 is both antiviral and antifungal. This project studies differences in the main Histatin members from a structural and behavioural perspective, using X-ray scattering (SAXS), Molecular Dynamics (MD) simulation, and Circular Dichroism (CD). Current SAXS data describe all three peptides as intrinsically disordered, with Hst1 and Hst3 showing signs of being partially ordered with salt dependency. MD simulations and CD data show a slight imprint of secondary structure elements with largely disordered behaviour. Based on SAXS, Hst1 could potentially self-associate, while Hst3 likely does not. Hst5 is known to refrain from self-associating. Hst3 and Hst5 share a lot of behavioural patterns but are not identical. Hst3, unlike Hst5, appears to expand in more concentrated environments based on the radius of gyration values derived from SAXS spectra.}},
author = {{Svensson, Oskar}},
language = {{eng}},
note = {{Student Paper}},
title = {{Histatins: Peptides with a license to kill}},
year = {{2024}},
}