# The structural basis of homo- and heterodimerization of two chemokine receptors: Implications in HIV-1 cell entry

> **NIH NIH R56** · BRIGHAM AND WOMEN'S HOSPITAL · 2021 · $758,083

## Abstract

SUMMARY
The chemokine receptors CCR5 and CXCR4 play essential roles in the human immune system and are
involved in HIV infection and cancer metastasis. Several studies have demonstrated the role of homo- and
heterodimerization of these receptors in modulating protein function by affecting their chemokine sensitivity or
altering their G protein coupling mechanisms. Moreover, the ability of HIV to infect T cells utilizing either
CXCR4 or CCR5 as a co-receptor has been shown to depend on homo- and heterodimerization.
Consequently, the association of these two chemokine receptors has increasingly gained attention for drug
design. At this time, there is no high-resolution structure available for CCR5 or CXCR4 homo- or heterodimers
due to the complexity of the crystallization and sample preparation for EM. In aim 1, we will study the
dimerization of CCR5 protein at both molecular and functional levels. In aim 2, we will study the
heterodimerization of CCR5 and CXCR4. In aim 3, we will develop a nanodisc-based fusion assay. Moreover,
we will image HIV pseudovirus particles binding and fusion with large nanodiscs containing CD4/CCR5 or
CD4/CXCR4.

## Key facts

- **NIH application ID:** 10455267
- **Project number:** 1R56AI150406-01A1
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Mahmoud Nasr
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $758,083
- **Award type:** 1
- **Project period:** 2021-08-20 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10455267

## Citation

> US National Institutes of Health, RePORTER application 10455267, The structural basis of homo- and heterodimerization of two chemokine receptors: Implications in HIV-1 cell entry (1R56AI150406-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10455267. Licensed CC0.

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