Evolution of an interaction between disordered proteins resulted in increased heterogeneity of the binding transition state

bioRxiv (Cold Spring Harbor Laboratory)

Abstract

Abstract Intrinsically disordered protein (IDP) domains often have multiple binding partners. Little is known regarding molecular changes in the binding mechanism when a new interaction evolves from low to high affinity. Here we compared the degree of native contacts in the transition state of the interaction of two IDP domains, low-affinity ancestral and high-affinity human NCBD and CID. We found that the coupled binding and folding mechanism of the domains is overall similar, but with a higher degree of native hydrophobic contact formation in the transition state of the ancestral complex while more heterogenous transient interactions, including electrostatic, and an increased disorder characterize the human complex. From an evolutionary perspective, adaptation to new binding partners for IDPs may benefit from this ability to exploit multiple alternative transient interactions while retaining the overall pathway.

Authors 9

1. Elin Karlsson

   Uppsala University

   Affiliation as printed

   Department of Medical Biochemistry and Microbiology, Uppsala University, BMC Box 582, SE-75123 Uppsala, Sweden

   Department of Medical Biochemistry and Microbiology, Uppsala University, BMC Box 582, SE-7523 Uppsala, Sweden

2. Cristina Paissoni

   University of Milan

   Affiliation as printed

   Dipartimento di Bioscienze, Università degli Studi di Milano, 20133 Milano, Italy

   Dipartimento di Bioscienze, Università degli Studi di Milano, 0133 Milano, Italy

3. Amanda M. Erkelens Aachen Department of Chemistry, Leiden University

   Leiden University · Uppsala University

   Affiliation as printed

   Department of Chemistry, Leiden University, Leiden, Netherlands

   Department of Medical Biochemistry and Microbiology, Uppsala University, BMC Box 582, SE-75123 Uppsala, Sweden

   Department of Medical Biochemistry and Microbiology, Uppsala University, BMC Box 582, SE-7523 Uppsala, Sweden

4. Zeinab Amiri‐Tehranizadeh

   Uppsala University · Mashhad University of Medical Sciences

   Affiliation as printed

   Department of Medical Biochemistry and Microbiology, Uppsala University, BMC Box 582, SE-75123 Uppsala, Sweden

   Department of Medicinal Chemistry, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

   Department of Medical Biochemistry and Microbiology, Uppsala University, BMC Box 582, SE-7523 Uppsala, Sweden

5. Frieda A. Sorgenfrei

   Uppsala University · University of Graz

   Affiliation as printed

   Department of Chemistry, Institute of Organic and Bioorganic Chemistry, University of Graz, Heinrichstraße 28, 8010 Graz, Austria

   Department of Medical Biochemistry and Microbiology, Uppsala University, BMC Box 582, SE-75123 Uppsala, Sweden

   Department of Medical Biochemistry and Microbiology, Uppsala University, BMC Box 582, SE-7523 Uppsala, Sweden

6. Eva Andersson

   Uppsala University

   Affiliation as printed

   Department of Medical Biochemistry and Microbiology, Uppsala University, BMC Box 582, SE-75123 Uppsala, Sweden

   Department of Medical Biochemistry and Microbiology, Uppsala University, BMC Box 582, SE-7523 Uppsala, Sweden

7. Weihua Ye

   Uppsala University

   Affiliation as printed

   Department of Medical Biochemistry and Microbiology, Uppsala University, BMC Box 582, SE-75123 Uppsala, Sweden

   Department of Medical Biochemistry and Microbiology, Uppsala University, BMC Box 582, SE-7523 Uppsala, Sweden

8. Carlo Camilloni corresponding

   University of Milan

   Affiliation as printed

   Dipartimento di Bioscienze, Università degli Studi di Milano, 20133 Milano, Italy

   Dipartimento di Bioscienze, Università degli Studi di Milano, 0133 Milano, Italy

9. Per Jemth corresponding

   Uppsala University

   Affiliation as printed

   Department of Medical Biochemistry and Microbiology, Uppsala University, BMC Box 582, SE-75123 Uppsala, Sweden

   Department of Medical Biochemistry and Microbiology, Uppsala University, BMC Box 582, SE-7523 Uppsala, Sweden