# Glycosylation and Biogenesis of Streptococcal Adhesins

> **NIH NIH R01** · OREGON HEALTH & SCIENCE UNIVERSITY · 2022 · $359,242

## Abstract

Essential to oral biofilm development is the initial colonization by oral streptococci. The abundant oral
streptococci keep pathogens at bay. We have used the most abundant oral streptococcus, Streptococcus
parasanguinis as a model to study bacterial colonization and identified a new family of bacterial serine-rich
repeat proteins (SRRPs) named “fimbriae-associated protein-1” (Fap1). Fap1 is heavily glycosylated, and
glycosylation of Fap1 is crucial for bacterial biofilm formation. Since our discovery of Fap1, Fap1-like SRRPs
have been identified from numerous Gram-positive bacteria and implicated in bacterial fitness and virulence.
Our studies have led to the groundbreaking discovery of a new Fap1 biosynthetic pathway. We have
demonstrated that the Fap1 biogenesis is controlled by a gene cluster encoding a series of novel
glycosyltransferases and unique accessory secretion proteins. Biogenesis of SRRPs has now emerged as a
new paradigm to investigate bacterial protein glycosylation and secretion. During our study of Fap1
glycosylation, we have defined a complete glycosylation pathway that synthesizes a novel Fap1 glycan. In the
study of Fap1 secretion, we have identified a protein complex consisting of three distinct glycosylation
associated proteins Gap1, 2 and 3 that work in concert to modulate the Fap1 maturation and biogenesis.
Further, we have determined the high resolution 3-dimensional structure of the Gap1/2/3 complex, which
uncovered new mechanistic insights for this 3-protein complex. Gap1 and Gap2 exhibit dual functions in the
biogenesis of Fap1. 1), Gap1 and Gap2 modulates the formation of the protein complex as a molecular
chaperone. 2), Gap1 and Gap2 function as a glucosyltransferase and glucosidase respectively in the quality
control of Fap1 maturation and biogenesis. The Gap protein complex resembles the three-key elements in the
eukaryotic quality control system dedicated to glycosylated proteins, hence we will continue our basic science
discovery of new biology and biochemistry linked to maturation and biogenesis of Fap1 & other SRRPs.
Aim 1 Determine how Gap1 functions as a molecular chaperone for Gap2 and as a key quality control
glycosyltransferase to process Fap1 precursor during Fap1 biogenesis. We will use genetic, biochemical,
structural biology, and glycobiology approaches to investigate how Gap1 stabilizes Gap2 as a molecular
chaperone, and how Gap1 acts as a quality control glycosyltransferase to process Fap1 precursor.
Aim 2 Define the roles played by Gap2 as a molecular chaperone for Gap3 and as a key quality control
glucosidase during Fap1 biogenesis. We will determine how Gap2 assists Gap3 as an accessory
chaperone, and coordinates with Gap1 and Gap3 to process Fap1, thus modulating the Fap1 biogenesis.
As biogenesis of SRRPs is highly conserved in Gram-positive bacteria, deciphering novel molecular insight to
this new protein complex as a quality control system will offer new opportunities to develop new strategi...

## Key facts

- **NIH application ID:** 10336503
- **Project number:** 5R01DE017954-16
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Hui Wu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $359,242
- **Award type:** 5
- **Project period:** 2020-08-03 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10336503

## Citation

> US National Institutes of Health, RePORTER application 10336503, Glycosylation and Biogenesis of Streptococcal Adhesins (5R01DE017954-16). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10336503. Licensed CC0.

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