Cation-induced intramolecular coil-to-globule transition in poly(ADP-ribose)

Tong Wang; Kush Coshic; Mohsen Badiee; Maranda R McDonald; Aleksei Aksimentiev; Lois Pollack; Anthony K L Leung

doi:10.1038/s41467-024-51972-9

Cation-induced intramolecular coil-to-globule transition in poly(ADP-ribose)

Nat Commun. 2024 Sep 10;15(1):7901. doi: 10.1038/s41467-024-51972-9.

Authors

Tong Wang^#¹, Kush Coshic^#², Mohsen Badiee^#³, Maranda R McDonald^{3

4}, Aleksei Aksimentiev^{5

6

7}, Lois Pollack⁸, Anthony K L Leung^{9

10

11

12

13}

Affiliations

¹ School of Applied and Engineering Physics, Cornell University, Ithaca, NY, 14853, USA.
² Center for Biophysics and Quantitative Biology, University of Illinois Urbana Champaign, Urbana, IL, 61801, USA.
³ Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, 21205, USA.
⁴ Chemistry-Biology Interface Graduate Program, Johns Hopkins University, Baltimore, MD, 21218, USA.
⁵ Center for Biophysics and Quantitative Biology, University of Illinois Urbana Champaign, Urbana, IL, 61801, USA. [email protected].
⁶ Beckman Institute for Advanced Science and Technology, University of Illinois Urbana Champaign, Urbana, IL, 61801, USA. [email protected].
⁷ Department of Physics, University of Illinois Urbana Champaign, Urbana, IL, 61801, USA. [email protected].
⁸ School of Applied and Engineering Physics, Cornell University, Ithaca, NY, 14853, USA. [email protected].
⁹ Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, 21205, USA. [email protected].
¹⁰ Chemistry-Biology Interface Graduate Program, Johns Hopkins University, Baltimore, MD, 21218, USA. [email protected].
¹¹ Department of Molecular Biology and Genetics, School of Medicine, Johns Hopkins University, Baltimore, MD, 21205, USA. [email protected].
¹² Department of Oncology, School of Medicine, Johns Hopkins University, Baltimore, MD, 21205, USA. [email protected].
¹³ Department of Genetic Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD, 21205, USA. [email protected].

^# Contributed equally.

Abstract

Poly(ADP-ribose) (PAR), a non-canonical nucleic acid, is essential for DNA/RNA metabolism and protein condensation, and its dysregulation is linked to cancer and neurodegeneration. However, key structural insights into PAR's functions remain largely uncharacterized, hindered by the challenges in synthesizing and characterizing PAR, which are attributed to its length heterogeneity. A central issue is how PAR, comprised solely of ADP-ribose units, attains specificity in its binding and condensing proteins based on chain length. Here, we integrate molecular dynamics simulations with small-angle X-ray scattering to analyze PAR structures. We identify diverse structural ensembles of PAR that fall into distinct subclasses and reveal distinct compaction of two different lengths of PAR upon the addition of small amounts of Mg²⁺ ions. Unlike PAR₁₅, PAR₂₂ forms ADP-ribose bundles via local intramolecular coil-to-globule transitions. Understanding these length-dependent structural changes could be central to deciphering the specific biological functions of PAR.

MeSH terms

Cations / chemistry
Humans
Magnesium / chemistry
Molecular Dynamics Simulation*
Poly Adenosine Diphosphate Ribose* / chemistry
Poly Adenosine Diphosphate Ribose* / metabolism
Scattering, Small Angle*
X-Ray Diffraction

Substances

Poly Adenosine Diphosphate Ribose
Magnesium
Cations

Abstract

MeSH terms

Substances

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