# Project 7:  RT-probed protein interaction study in solution

> **NIH NIH P50** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2020 · $232,230

## Abstract

P7. Abstract
This project aims to site-specifically characterize transient interactions between HIV-1 reverse transcriptase
(RT) and its binding partners by solution NMR and to investigate the effects of such interactions on the
dynamics of the interacting system. Solution NMR studies of RT and complexes thereof are challenging, given
the size of the RT heterodimer. This necessitates developing and applying new methodological approaches
suited for investigations of large molecular complexes. While the current RT X-ray structures provide
important insights into how RT interacts with drugs and substrate, they are static snapshots of a subset of
conformational states captured through crystallization. These structures do not inform on the motions within
the protein or complex, which are critically connected to its functions. In this project, we will fill the existing
knowledge gap and determine the functionally important dynamics in RT. Specifically, we will i) identify which
domains and residues of RT are involved in the interaction with Integrase (IN); ii) delineate specifically the
intermolecular contacts on RT and determine the RT/IN dynamics; and iii) determine the biological
significance of structural or dynamics changes in RT upon IN and nucleic acid binding. To accomplish the
specific aims of this project, we will employ a multi-pronged approach encompassing solution NMR as well as
enzymology and virology studies. We will combine the complementary expertise of the PCHPI investigators
and collaborators and work in close synergy to tackle the important questions concerning the role of dynamics
in RT for HIV infection.

## Key facts

- **NIH application ID:** 9977959
- **Project number:** 5P50AI150481-14
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** RIEKO ISHIMA
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $232,230
- **Award type:** 5
- **Project period:** 2007-08-27 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9977959

## Citation

> US National Institutes of Health, RePORTER application 9977959, Project 7:  RT-probed protein interaction study in solution (5P50AI150481-14). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9977959. Licensed CC0.

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