Publications

PREPRINTS

Novel mechanisms of MITF regulation and melanoma predisposition identified in a mouse suppressor screen

Vua HN, Valdimarsson MM, Sigurbjörnsdóttir S, Bergsteinsdóttir K, Debbache J, Bismuth K, Swing DA, Hallsson JH, Larue L, Arnheiter H,Copeland NG, Jenkins NA, Heidarsson PO, and Steingrímsson E (2023) BioRxiv, https://doi.org/10.1101/2023.08.04.551952.

DNA binding redistributes activation domain ensemble and accessibility in pioneer factor Sox2 

Bjarnason S, McIvor JAP, Prestel A, Demény KS, Bullerjahn JT, Kragelund BB, Mercadante D, and Heidarsson PO (2024) Nat Commun 15, 1445.(PDF)

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PED in 2024: Improving the community deposition of structural ensembles for intrinsically disordered proteins

Ghafouri H, Lazar T, Del Conti A, Ku LGT, PED Consortium, Tompa P, Tosatto SCE, Monzon AM (2023) Nucleic Acids Res, gkad947, https://doi.org/10.1093/nar/gkad947. (PDF)

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Human small heat-shock protein B8 inhibits protein aggregation without affecting the native folding process

Choudhary D, Mediani L, Avallaneda MJ, Bjarnason S, Alberti S, Boczek EE, Heidarsson PO, Mossa A, Carra S, Tans SJ, Cecconi C (2023) J Am Chem Soc 145(28), 15188-15196. (PDF)

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Multifunctional intrinsically disordered regions in transcription factors

Már M, Nitsenko K & Heidarsson PO (2023)Chemistry – A European Journal, doi:10.1002/chem.202203369. (PDF)

 

The chemical features of intrinsically disordered regions in transcription factors that endow them with structural plasticity central to their functions are dissected in this Review. We highlight recent studies that illustrate the involvement of disordered regions in processes such as protein interactions, DNA binding and specificity, chromatin opening, and phase separation. 

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Release of linker histone from the nucleosome driven by polyelectrolyte competition with a disordered protein

Heidarsson PO, Mercadante D, Sottini A, Nettels D, Borgia M, Borgia A, Kilic S, Fierz B, Best RB, Schuler B (2022) Nat Chem 14, 224-231. (PDF)

 

In this paper we show that histone H1 binds nucleosomes fast and tight yet remains disordered, allowing a disordered chaperone to facilitate dissociation by forming a ternary complex. 

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Protein intrinsic disorder on a dynamic nucleosomal landscape

Bjarnason S, Ruidiaz SF, McIvor J, Mercadante D, and Heidarsson PO, (2021) Prog Mol Biol Transl Sci 183, 295-354.

 

In this chapter we present and discuss the crucial role of disordered interactions in the nuclear milieu. (PDF)

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From folding to function: Complex macromolecular reactions unraveled one-by-one with optical tweezers

Heidarsson PO, Cecconi C (2021) Essays Biochem, EBC20200024. doi: 10.1042/EBC20200024. Epub ahead of print. PMID: 33438724.

 

This mini-review explains the basic principles of optical tweezers and highlights some recent studies on complex biological phenomena. (PDF)

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Polyelectrolyte interactions enable rapid association and dissociation in high-affinity disordered protein complexes

Sottini A, Borgia A, Borgia M, Bugge K, Nettels D, Chowdhury A, Heidarsson PO, Zosel F, Best RB, Kragelund BB, Schuler B (2020) Nat Commun 11, 5736.

 

The highly disordered complex between histone H1 and prothymosin alpha switches from slow to fast association/dissociation kinetics with higher concentrations due to formation of transient ternary complexes, keeping this regulatory system highly responsive despite extremely high affinites. (PDF)

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Effects of Ligand Binding on the Energy Landscape of Acyl-CoA-Binding Protein

Sonar P, Bellucci L, Mossa A, Heidarsson PO, Kragelund BB, Cecconi C (2020) Biophys J 119(9), 1821-1832.

 

Using the well-studied acyl-CoA binding protein, we show that the protein retains its unusual deformability after binding a natural ligand, which may be important for its transporting functions. (PDF)

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DISORDER IN A TWO-DOMAIN NEURONAL CA 2+-BINDING PROTEIN REGULATES DOMAIN STABILITY AND DYNAMICS USING LIGAND MIMICRY

Staby L, Kemplen KR, Stein A, Ploug M, Clarke J, Skriver K, Heidarsson PO, Kragelund BB (2020) Cell Mol Life Sci 78, 2263–2278.

 

An investigation on the interplay of order and disorder in neuronal calcium sensor-1 reveals a critical ligand-mimicking motif for order-disorder communication. (PDF)

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BINDING WITHOUT FOLDING- THE BIOMOLECULAR FUNCTION OF DISORDERED POLYELECTROLYTE COMPLEXES

Schuler B, Borgia A, Borgia M, Heidarsson PO, Holmstrom ED, Nettels D, Sottini A (2020) Curr Opin Struct Biol 60, 66-76.

 

A review article about the emerging principles of IDP binding without folding and future perspectives of merging experiment and simulations to tackle these systems. (PDF)

THE COMPLEX CONFORMATIONAL DYNAMICS OF A NEURONAL CALCIUM SENSOR: A SINGLE MOLECULE PERSPECTIVE

Choudhary D, Kragelund BB, Heidarsson PO, Cecconi C (2018) Front Mol Neurosci 11, 1-8.

 

This review summarizes what we have learned about the folding of a neuronal calcium sensor protein on the single-molecule level. (PDF)

Extreme disorder in an ultrahigh-affinity protein complex

Borgia A, Borgia M, Bugge K, Kissling VM, Heidarsson PO, Fernandez CB, Sottini A, Soranno A, Bucholzer KJ, Nettels D, Kragelund BB, Best RB, Schuler B (2018) Nature 555, 61-66.    


Here we reveal a novel interaction mechanism for proteins: Two oppositely charged disordered proteins form a picomolar-affinity complex yet remain fully disordered and dynamic.

See News & Views by Berlow & Wright (2018): “Tight complexes from disordered proteinsNature 555, 37-38. (PDF)

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SINGLE-MOLECULE FOLDING MECHANISMS OF THE APO AND MG2+-BOUND STATES OF HUMAN NEURONAL CALCIUM SENSOR-1

Naqvi MM, Heidarsson PO, Otazo MR, Mossa A, Kragelund BB, Cecconi C (2015) Biophys J 109(1), 113-123.   

Front cover of issue showcased our paper. (PDF)

heidarsson pnas 2014

DIRECT SINGLE-MOLECULE OBSERVATION OF CALCIUM-DEPENDENT MISFOLDING IN HUMAN NEURONAL CALCIUM SENSOR-1

Heidarsson PO, Naqvi MM, Otazo MR, Mossa A, Kragelund BB, Cecconi C (2014) Proc Natl Acad Sci USA 111(36), 13069-13074. (PDF)

Erlendsson 2015

PICK1 PROMISCUITY RELIES ON ALTERNATING BINDING MODES FOR NON-TYPE II PDZ DOMAIN LIGANDS

Erlendsson S, Rathje M, Heidarsson PO, Poulsen FM, Madsen KL, Teilum K and Gether U (2014) J Biol Chem 289(36), 25327-25340. (PDF)

Ozenne 2015

EXPLORING THE MINIMALLY FRUSTRATED ENERGY LANDSCAPE OF UNFOLDED ACBP

Ozenne V, Noel J, Heidarsson PO, Brander S, Poulsen FM, Ringkjøbing-Jensen M, Kragelund BB, Blackledge M, Danielsson J (2014) J Mol Biol 426(3), 722-734. (PDF)

heidarsson 2014

SINGLE-MOLECULE FOLDING MECHANISM OF AN EF-HAND NEURONAL CALCIUM SENSOR

Heidarsson PO, Otazo MR, Bellucci L, Mossa A, Imparato A, Paci E, Corni S, Di Felice R, Kragelund BB, Cecconi C (2013) Structure 21, 1812-1821. (PDF)

kenchappa 2012

SOLUTION PROPERTIES OF THE ARCHAEAL CRISPR DNA REPEAT-BINDING HOMEODOMAIN PROTEIN CBP2

Kenchappa CS, Heidarsson PO, Kragelund BB, Garrett RA, Poulsen FM (2013) Nucl Acids Res 4, 3424-3435. (PDF)

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CONFORMATIONAL DYNAMICS OF SINGLE PROTEIN MOLECULES STUDIED WITH DIRECTED MECHANICAL MANIPULATION

Heidarsson PO, Naqvi MN, Sonar P, Valpapuram I, Cecconi C (2013) Adv Protein Chem Struct Biol 92, 93-133. (PDF)

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A HIGHLY COMPLIANT PROTEIN NATIVE STATE WITH A SPONTANEOUS-LIKE MECHANICAL UNFOLDING PATHWAY

Heidarsson PO, Valpapuram I, Camilloni C, Imparato M, Tiana G, Poulsen FM, Kragelund BB, Cecconi C (2012) J Am Chem Soc 134(41), 17068-17065. (PDF)

THE C-TERMINAL TAIL OF HUMAN NEURONAL CALCIUM SENSOR 1 REGULATES THE CONFORMATIONAL STABILITY OF THE CA2+ ACTIVATED STATE

Heidarsson PO, Bjerrum-Bohr I, Jensen GA, Pongs O, Finn BE, Poulsen FM, Kragelund BB (2012) J Mol Biol 417, 51-64. (PDF)

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EXPLORING FOLDING PATHWAYS OF SINGLE PROTEINS USING MECHANICAL MANIPULATION

Heidarsson PO and Cecconi C (2012) AIP Conf Proc 1456, 201-206. (PDF)

heidarsson epr paper

STRUCTURAL FEATURES AND DYNAMICS OF A COLD-ADAPTED ALKALINE PHOSPHATASE STUDIED WITH EPR SPECTROSCOPY

Heidarsson PO, Sigurdsson ST, Ásgeirsson B (2009) FEBS J 276, 2725-2735. (PDF)

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EFFECT OF ACTIVE SITE MUTATION ON CATALYSIS AND BACKBONE DYNAMICS IN A COLD-ADAPTED ENZYME

Heidarsson PO and Ásgeirsson B (2009) Raust-Journal of applied sciences
and mathematics 6, 79-85 (in Icelandic).