# Molecular mechanisms for the evolution of the total peptide binding set in S100 proteins

> **NIH NIH R01** · UNIVERSITY OF OREGON · 2020 · $289,476

## Abstract

PROJECT SUMMARY
The long-term goal of this project is to understand the ability of the proteins S100A5 and S100A6 to bind to
and recognize their target proteins. S100A5 and S100A6 are small proteins that bind to downstream target
proteins in the cell in response to calcium; however, the precise targets remain poorly understood. S100A5 and
S100A6 are both upregulated in disease states, including various cancers and heart disease; however, not
knowing their binding partners hampers efforts to understand the causes or consequences of this effect.
The first goal of the project is to identify possible binding targets using “phage display,” an approach for
identifying short protein fragments that may bind to the protein. This approach, while powerful, is also
plagued by false positive rates. To get around this, the project is guided by the words of a famous geneticist:
“nothing in biology makes sense except in light of evolution.” This means that averaging phage display/binding
results from the human proteins versus other animals amplifies the signal of biologically important protein
fragments. The second goal is to identify the pieces on S100A5 and S100A6 that are important for its
interactions with its possible targets. Revealing the evolutionary path by which a protein acquired its current
protein targets efficiently reveals the residues responsible and thus sets up mechanistic studies of its binding.

## Key facts

- **NIH application ID:** 10000935
- **Project number:** 5R01GM117140-05
- **Recipient organization:** UNIVERSITY OF OREGON
- **Principal Investigator:** Michael Jonathan Harms
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $289,476
- **Award type:** 5
- **Project period:** 2016-09-01 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10000935

## Citation

> US National Institutes of Health, RePORTER application 10000935, Molecular mechanisms for the evolution of the total peptide binding set in S100 proteins (5R01GM117140-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10000935. Licensed CC0.

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