University of Oulu

Oda C. Krokengen, Arne Raasakka, Petri Kursula, The intrinsically disordered protein glue of the myelin major dense line: Linking AlphaFold2 predictions to experimental data, Biochemistry and Biophysics Reports, Volume 34, 2023, 101474, ISSN 2405-5808,

The intrinsically disordered protein glue of the myelin major dense line : linking AlphaFold2 predictions to experimental data

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Author: Krokengen, Oda C.1; Raasakka, Arne1; Kursula, Petri1,2
Organizations: 1Department of Biomedicine, University of Bergen, Norway
2Faculty of Biochemistry and Molecular Medicine & Biocenter Oulu, Oulu, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 6.8 MB)
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Language: English
Published: Elsevier, 2023
Publish Date: 2023-09-20


Numerous human proteins are classified as intrinsically disordered proteins (IDPs). Due to their physicochemical properties, high-resolution structural information about IDPs is generally lacking. On the other hand, IDPs are known to adopt local ordered structures upon interactions with e.g. other proteins or lipid membrane surfaces. While recent developments in protein structure prediction have been revolutionary, their impact on IDP research at high resolution remains limited. We took a specific example of two myelin-specific IDPs, the myelin basic protein (MBP) and the cytoplasmic domain of myelin protein zero (P0ct). Both of these IDPs are crucial for normal nervous system development and function, and while they are disordered in solution, upon membrane binding, they partially fold into helices, being embedded into the lipid membrane. We carried out AlphaFold2 predictions of both proteins and analysed the models in light of experimental data related to protein structure and molecular interactions. We observe that the predicted models have helical segments that closely correspond to the membrane-binding sites on both proteins. We furthermore analyse the fits of the models to synchrotron-based X-ray scattering and circular dichroism data from the same IDPs. The models are likely to represent the membrane-bound state of both MBP and P0ct, rather than the conformation in solution. Artificial intelligence-based models of IDPs appear to provide information on the ligand-bound state of these proteins, instead of the conformers dominating free in solution. We further discuss the implications of the predictions for mammalian nervous system myelination and their relevance to understanding disease aspects of these IDPs.

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Series: Biochemistry and biophysics reports
ISSN: 2405-5808
ISSN-E: 2405-5808
ISSN-L: 2405-5808
Volume: 34
Article number: 101474
DOI: 10.1016/j.bbrep.2023.101474
Type of Publication: A1 Journal article – refereed
Field of Science: 1182 Biochemistry, cell and molecular biology
Funding: This work was funded through a FRIPRO grant (324877) from the Research Council of Norway (to PK).
Copyright information: © 2023 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (