We study interactions between proteins and other biomolecules. For example, we have found a new type of protein interactions that does not follow any known rules of protein:protein interactions. In addition, we also study protein aggregation into disease related amyloid fibrils, and why a protein from Brazil nut is only allergenic in a complex with a fatty acid.
Proteins are one of the most important key players in a cell. In accordance with their unique three-dimensional structures they have a variety of different functions, such as protections against viruses and other pathogens (anti bodies), catalyst of chemical reactions (enzymes), control of synthesis of new proteins (transcription factors) etc. In addition, many proteins are only active if the interact with other molecules. It is therefore not surprising that the faith of a cell in large depends on how proteins interacts with each other or with other molecules. Our research is focused on how proteins interact with each other and other biomolecules. This can occur in a correct way, but also in an incorrect, disease related way. We are interested in both cases. To study this we focus on three different projects, all with protein interactions a s a general theme. For example, we have recently been able to characterize a complete new type of protein:protein interaction that does not follow any known fundamental principles of protein interactions. We also study why some proteins start to aggregates into large amyloid fibrils, causing amyloidogenic diseases such as Alzheimer disease, Creutzfeldt-Jacob disease etc. In addition, we try to find out the reason why only a complex between a protein and an other molecule from Brazil nut is causing food allergy, but not the individual components alone.
This research proposal involves three projects where the focus of research is on interaction between biomolecules using advanced biophysical and biochemical methods.
Project I, Ber e 1: The brazil nut protein Ber e 1 is the first known case where only a protein in complex with an other molecule is allergenic, not their respective components alone. The aim of this project is to define structural properties of Ber e 1 in absence and presence of this other molecule in order to uncover the requirements of an allergenic macromolecule. To achieve this we will: (i) Determine the solution structure of Ber e 1, and (ii) Characterize the binding properties of the other molecule and map the binding surface of Ber e 1 using NMR. Spectroscopy.
Project II, amyloid: The aim of this project is to determine factors involved in aggregation of proteins into amyloid fibrils. To reach these goals we intend to use multivariate analysis to investigate intrinsic properties of different amino acids and their influence on amyloid aggregation, and (ii) use fluorescence spectroscopy to investigate what part of the proteins that are involved in the formation of these highly ordered fibrils.
Project III, Calmodulin: The specific aim of this project is to characterize a new type of protein recognition that we recently discovered in the complex between calmodulin (CaM) and basic-Helix-Loop-Helix (bHLH) transcription factors. At present, very little is known about the dynamic behaviour of the bHLH proteins within the complex. To characterize the dynamic behaviour and elucidate the energetic terms in the CaM:bHLH interaction we therefore intend to: Express a 15N labelled fusion protein which express the CaM binding region of the bHLH protein SEF2-1. This will enable us to study the dynamics of a bHLH mimicking peptide with NMR relaxation experiments.