Electron Micrograph of Islet Amyloid Polypeptide Fibrils (x 60,000)
Research Projects
My research involves using biophysical techniques such electron paramagnetic resonance spectroscopy (EPR), fluorescence spectroscopy, and circular dichroism (CD) spectroscopy to investigate the structure and membrane association of polypeptides. I am particularly interested in (a). determining the sequence and structural characteristics that govern the aggregation properties of the Islet Amyloid Polypeptide (IAPP), and (b). determining the membrane bound and solution structures and conformational changes of the C-reactive protein (CRP).
Sequence and structural characteristics that govern the aggregation of IAPP.
The misfolding, aggregation and fibril formation of the 37-residue Islet Amyloid Polypeptide (IAPP) is thought to play a vital role in the pathogenesis of type II diabetes. IAPP belongs to the Calcitonin Gene Related Peptide (CGRP) superfamily, to which Calcitonin and the Calcitonin Gene Related Peptide (CGRP) also belong. Although IAPP and CGRP share significant sequence similarity CGRP has not shown to aggregate. What sequence and structural features prevent the aggregation of CGRP? Like IAPP Calcitonin is also known to aggregate and form amyloid fibrils. Does Calcitonin adopt a structure similar to that of IAPP in the fibrilar form? Does Calcitonin interact with membranes in a manner similar to IAPP? Answers to such questions may help us understand the molecular details that govern the aggregation of IAPP, and may also help us understand the mechanistic details of polypeptide aggregation in general.
The membrane bound and solution structures and conformational changes of the C-reactive protein.
PUBLICATIONS
JOURNAL ARTICLES
Jayasinghe, S.A.,
and Langen, R., Membrane Interaction of Islet Amyloid
Polypeptide, Biochim. Biophys. Acta, 2007 February 6
(Electronic Publication Ahead of Print).
Meier, J.J., Kayed, R., Lin, C.Y., Gurlo, T., Haataja, L.,
Jayasinghe, S., Langen, R., Glabe, C.C., Butler, P.C.,
(2006), Inhibition of hIAPP fibril formation does not
prevent beta-cell death: Evidence for distinct actions of
oligomers and fibrils of hIAPP. American Journal
of Physiology - Endocrinology and
Metabolism, 291(6), 2006 July
18 (Electronic Publication Ahead of Print).
Jayasinghe, S.A.,
and Langen R., (2005). Lipid Membranes Modulate the
Structure of Islet Amyloid Polypeptide, Biochemistry,
44(13):12113-12119.
Jayasinghe, S.A., and Langen R., (2004). Identifying
structural features of fibrillar islet amyloid polypeptide
using site-directed spin labeling. Journal of Biological
Chemistry, 279:48420-48425.
Ellena, J.F., Moulthrop J., Wu, J., Rauch, M., Jayasinghe,
S., Castle, J.D., and Cafiso, D.S., (2004). Membrane
position of a basic aromatic peptide that sequesters
phosphatidylinositol 4,5 bisphosphate determined by
site-directed spin labeling and high-resolution NMR.
Biophysical Journal, 87:3221-3233.
Isas, J.M., Patel, D.R., Jao, C., Jayasinghe, S.,
Cartailler, J.P., Haigler, H.T., and Langen, R.(2003).
Global structural changes in annexin 12- The role of
phospholipids, Ca2+, and pH. Journal of Biological
Chemistry, 278:30227-30234.
Jayasinghe, S., Hristova, K., and White, S.H. (2001).
Transmembrane helix energetics and prediction accuracy.
Journal of Molecular Biology, 312:927-934.
Jayasinghe, S., Hristova, K., and White, S.H. (2001).
MPtopo: A database of membrane protein topology. Protein
Science, 10:455-458.
White, S.H., Ladokhin, A.S., Jayasinghe, S., and Hristova,
K. (2001). How membranes shape protein structure. Journal
of Biological Chemistry, 276:32395-32398.
Ladokhin, A.S., Jayasinghe, S., and White, S.H. (2000). How
to measure and analyze tryptophan fluorescence in membranes
properly, and why bother? Analytical Biochemistry,
285:235-245.
Hubbard, C., Singleton, D., Rauch, M., Jayasinghe, S.,
Cafiso, D., and Castle, D. (2000). The secretory carrier
membrane protein family: Structure and membrane topology.
Molecular Biology of the Cell, 11:2933-2947.
Jayasinghe, S., Barranger-Mathys, M., Ellena, J.F.,
Franklin, C., and Cafiso, D.S. (1998). Structural features
that modulate the transmembrane migration of a hydrophobic
peptide in lipid vesicles. Biophysical Journal,
74:3023-3030.
Franklin, J.C., Ellena, J.F., Jayasinghe, S., Kelsh, L.P.,
and Cafiso, D.S. (1994). The structure of
micelle-associated alamethicin from 1H NMR. Evidence for
conformational heterogeneity in a voltage-gated peptide.
Biochemistry, 33:4036-4035.
ABSTRACTS
Jayasinghe, S., and
Langen R., (2004). Lipid membranes modulate human islet
amyloid polypeptide aggregation. Protein
Science, 13.
Jayasinghe, S., Apostolidou, M., and Langen, R. (2004).
Characterizing Fibrillar Human Islet Amyloid Polypeptide
(IAPP). Biophysical
Journal, 86.
Jayasinghe, S., Torok, M., and Langen, R. (2003).
Interaction of Islet Amyloid Polypeptide with phospholipids
vesicles. Biophysical
Journal, 84.
Jayasinghe, S., and White, S.H. (2001). Partitioning of
peptides at the bilayer interface: The role of helicity and
pattern of hydrophobicity. Biophysical
Journal, 80:A2431.
Jayasinghe, S., Sacha, S., Castle, J.D., and Cafiso, D.S.
(2000). Phosphoinositide interactions of a peptide from a
secretory carrier membrane protein. Biophysical
Journal, 78:A2439.
Jayasinghe, S., Hristova, K., and White, S.H. (2000). MPEx
and MPtopo: Tools for membrane protein topology
analysis. Biophysical
Journal, 78:A930.
Frazier, A., Hinderliter, A., Jayasinghe, S., Almeida, P.,
Biltonen, R., Creutz, C., and Cafiso, D.(1999).
Investigation of the influence of basic peptides on acidic
lipid rearrangement in vesicles. Biophysical
Journal, 76:A213.