RESEARCH: TYROSINE PHOSPHATASE S
FOLDING PROJECT #18426 PROFILE

This project studies tiny protein pieces called 'wedge peptides' that help nerve cells grow back after injury. Scientists are using computer simulations to design better versions of these peptides that can get into cells more easily. The goal is to develop new treatments for diseases like spinal cord injuries.

Note: This TLDR is a simplication and may not be 100% accurate.

Protein tyrosine phosphatase S (PTPσ) plays an important signaling role in neuronal regeneration.

The so-called “wedge domain” of PTPσ is a 24-mer helix-loop-helix motif found in the intracellular D1 domain of the native protein.

Peptide constructs based on the wedge domain have been shown to inhibit PTPσ phosphatase activity, which promotes neuronal regeneration.
The simulations in this project are aimed at understanding the conformational dynamics of wedge peptides in solution, towards designing stapled peptide variants with improved affinity and cell permeability.

The long-term goal of this research is to develop therapeutics for neuronal degeneration diseases and spinal cord injuries.

This work is a collaboration with the Wang group at Temple University.
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Protein tyrosine phosphatase S

An enzyme that removes phosphate groups from tyrosine residues on proteins.

Protein tyrosine phosphatases (PTPs) are enzymes that play a crucial role in regulating various cellular processes by removing phosphate groups from tyrosine amino acids on proteins. PTPs are involved in signal transduction, cell growth and differentiation, and other important biological functions.

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PTPσ

Protein tyrosine phosphatase sigma

PTPσ is a specific type of protein tyrosine phosphatase that plays a vital role in neuronal regeneration. It helps in the repair and regrowth of nerve cells after injury.

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Wedge domain

A 24-mer helix-loop-helix motif found in the intracellular D1 domain of PTPσ.

The wedge domain is a specific structural region within the PTPσ protein. Its unique shape and amino acid composition allow it to interact with other proteins and regulate PTPσ's activity.

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Stapled peptide

A type of synthetic peptide with a covalent bond linking two amino acids in the backbone.

Stapled peptides are engineered to improve their stability and resistance to degradation. They can act as drug candidates by mimicking natural peptides and interacting with specific targets in the body.

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Neuronal degeneration

The progressive loss of nerve cells in the brain or spinal cord.

Neuronal degeneration refers to the gradual deterioration and death of neurons. This process can lead to a variety of neurological disorders, such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis (ALS).

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Spinal cord injuries

Damage to the spinal cord that can result in paralysis or other neurological impairments.

Spinal cord injuries occur when there is damage to the spinal cord, often due to trauma. These injuries can disrupt the transmission of nerve signals between the brain and the rest of the body, leading to various disabilities.