# Complexes of HMO1 with DNA: Structure and Affinity

## TL;DR

This paper investigates how the HMO1 protein binds to specific DNA sequences, revealing structural and affinity details that explain its sequence specificity.

## Contribution

The study provides new structural and thermodynamic insights into HMO1's DNA binding mechanism and its preference for the IFHL motif.

## Key findings

- HMO1 forms a complex with DNA without altering the structure of either component.
- Molecular modeling shows two extended sites on HMO1 Box B stabilize DNA bending.
- HMO1 binds IFHL sequences with twice the stability compared to randomized sequences.

## Abstract

Saccharomyces cerevisiae HMO1 is an architectural nuclear DNA-binding protein that stimulates the activity of some remodelers and regulates the transcription of ribosomal protein genes, often binding to a DNA motif called IFHL. However, the molecular mechanism dictating this sequence specificity is unclear. Our circular dichroism spectroscopy studies show that the HMO1:DNA complex forms without noticeable changes in the structure of DNA and HMO1. Molecular modeling/molecular dynamics studies of the DNA complex with HMO1 Box B reveal two extended sites at the N-termini of helices I and II of Box B that are involved in the formation of the complex and stabilize the DNA bend induced by intercalation of the F114 side chain between base pairs. A comparison of the affinities of HMO1 for 24 bp DNA fragments containing either randomized or IFHL sequences reveals a twofold increase in the stability of the complex in the latter case, which may explain the selectivity in the recognition of the IFHL-containing promoter regions.