Welcome
Welcome to the website of the Van der Wel research group, focusing on biological application of solid-state NMR methodology for the study of diverse membrane and amyloid systems. Please find more information below and under the various links to the left and above, or contact me by e-mail with any questions or comments you may have!
Research Interests
Our interests are in the application of solid state NMR to biological structure determination. Biological ssNMR allows measurements of structural and motional features of (partially) immobilized biomolecules, and is of particular interest due to its ability to access such information in a site-specific manner without requiring solublity or crystallinity.
Various human disorders involve the misfolding of proteins into fibrillar aggregates (including diseases like Huntington and Alzheimer’s), and one of the research aims is to address the structure and formation of these amyloid fibril aggregates. Furthermore, in the cells many proteins are immobilized (in their functional and active state) by being associated with or embedded in lipid bilayers that make up biological membranes. Such membrane-associated proteins and protein complexes are involved in a range of essential functions, such as membrane receptor proteins (common targets for pharmaceuticals). Our interests are in the interplay between the lipids in the membrane and the bound membrane proteins, and how this interaction affects protein-protein interactions. Interestingly, this has been found to be a two-way process that can control and affect both the functioning of the proteins and the behavior of the membrane.
Addressing these topics relies on a combination of various solid state NMR methodologies and complementary techniques. The links to the left address some of these topics. Some of these pages also highlight some of my previous work, using different experimental SSNMR approaches. It shows how SSNMR enables structural measurements on (micro)crystalline and fibrillar polypeptide aggregates, and gives atomic-level insight into protein-lipid interactions.
Selected Publications (see here for a complete listing)
- Amyloid-like fibrils from a domain-swapping protein feature a parallel, in-register conformation without native-like interactions.
Li, j.; Hoop, C.L.; Kodali, R.; Sivanandam, V.N.,; and Van der Wel, P.C.A.* (2011) J. Biol. Chem. 286(33): 28988-95 [at journal][PubMed] - The Aggregation-Enhancing Huntingtin N-terminus is Helical in Amyloid Fibrils
Sivanandam, V.N., Jayaraman, M., Hoop, C.L., Kodali, R., Wetzel, R., and Van der Wel, P.C.A. (2011) J. Am. Chem. Soc. 133(12): 4558–4566 [at journal] - Structural Characterization of GNNQQNY Amyloid Fibrils by Magic Angle Spinning NMR.
Van der Wel, P.C.A.; Lewandowski, J.R., and Griffin, R.G. (2010) Biochemistry 49(44): 9457–9469 on-line PubMed - Targeted 13C-13C Distance Measurements in a Microcrystalline Protein via J-Decoupled Rotational Resonance Width Measurements.
Van der Wel, P.C.A.; Eddy, M.T.; Ramachandran, R., and Griffin, R.G. (2009) ChemPhysChem 10 (9-10): 1656-1663 DOI - Observation of a low-temperature, dynamically driven structural transition in a polypeptide by solid state NMR spectroscopy
Bajaj, V.S.; Van der Wel, P.C.A., and Griffin, R.G. (2009) J. Am. Chem. Soc. 131 (1): 118–128 Online - Solid state NMR study of amyloid nanocrystals and fibrils formed by the peptide GNNQQNY from yeast prion protein Sup35p.
Van der Wel, P.C.A.; Lewandowski, J.R., and Griffin, R.G. (2007) J. Am. Chem. Soc. 129(16): 5117-5130 Online DOI
- Orientation and motion of tryptophan interfacial anchors in membrane-spanning peptides.
Van der Wel, P.C.A.; Reed, N.D.; Greathouse, D.V., and Koeppe, R.E., II (2007) Biochemistry 46(25):7514-24 AbstractDOI - Dynamic nuclear polarization of amyloidogenic peptide nanocrystals: GNNQQNY, a core segment of the yeast prion protein Sup35p.
Van der Wel, P.C.A.; Hu, K.-N.; Lewandowski, J.R., and Griffin, R.G. (2006) J. Am. Chem. Soc. 128(33):10840-10846 Abstract DOI - Geometry and intrinsic tilt of a tryptophan anchored membrane spanning peptide by 2H NMR.
Van der Wel, P.C.A.; Strandberg, E.; Killian, J.A., and Koeppe, R.E., II (2002) Biophys. J. 83(3): 1479-1488 Abstract Full Text - Tryptophan-anchored transmembrane peptides promote formation of nonlamellar phases in phosphatidylethanolamine model membranes in a mismatch-dependent manner.
Van der Wel, P.C.A.; Pott, T.; Morein, S.; Greathouse, D.V.; Koeppe II, R.E., and Killian, J.A. (2000) Biochemistry 39: 3124-33. Abstract DOI