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Science 325 (5938): 328-332

Copyright © 2009 by the American Association for the Advancement of Science

Functional Amyloids As Natural Storage of Peptide Hormones in Pituitary Secretory Granules

Samir K. Maji,1,* Marilyn H. Perrin,2 Michael R. Sawaya,3 Sebastian Jessberger,4 Krishna Vadodaria,4 Robert A. Rissman,5 Praful S. Singru,6 K. Peter R. Nilsson,7 Rozalyn Simon,7 David Schubert,8 David Eisenberg,3 Jean Rivier,2 Paul Sawchenko,2 Wylie Vale,2 Roland Riek1,9,{dagger}

Abstract: Amyloids are highly organized cross–β-sheet–rich protein or peptide aggregates that are associated with pathological conditions including Alzheimer’s disease and type II diabetes. However, amyloids may also have a normal biological function, as demonstrated by fungal prions, which are involved in prion replication, and the amyloid protein Pmel17, which is involved in mammalian skin pigmentation. We found that peptide and protein hormones in secretory granules of the endocrine system are stored in an amyloid-like cross–β-sheet–rich conformation. Thus, functional amyloids in the pituitary and other organs can contribute to normal cell and tissue physiology.

1 Laboratory of Physical Chemistry, Eidgenössische Technische Hochschule (ETH) Zürich, Wolfgang-Paulistrasse 10, CH-8093 Zürich, Switzerland.
2 Clayton Foundation Laboratories for Peptide Biology, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
3 Howard Hughes Medical Institute, UCLA-DOE Institute for Genomics and Proteomics, Box 951570, University of California, Los Angeles, CA 90095, USA.
4 Institute of Cell Biology, Department of Biology, ETH Zürich, 8093 Zürich, Switzerland.
5 Department of Neuroscience, University of California, San Diego, La Jolla, CA 92093, USA.
6 Division of Endocrinology, Diabetes and Metabolism, Tufts Medical Center, Boston, MA 02111, USA.
7 Department of Chemistry, IFM, Linköping University, SE-581 83 Linköping, Sweden.
8 Cellular Neurobiology Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
9 Structural Biology, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.

* Present address: School of Bioscience and Bioengineering, IIT Bombay, Powai, Mumbai 400076, India.

{dagger} To whom correspondence should be addressed. E-mail: roland.riek{at}phys.chem.ethz.ch


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