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J Struct Biol. 2018 Jul;203(1):27-36. doi: 10.1016/j.jsb.2018.02.008. Epub 2018 Mar 1.

αCGRP, another amyloidogenic member of the CGRP family.

Author information

1
Section of Cell Biology and Biophysics, Department of Biology, School of Sciences, National and Kapodistrian University of Athens, Panepistimiopolis, Athens 157 01, Greece. Electronic address: etsiolaki@biol.uoa.gr.
2
Section of Cell Biology and Biophysics, Department of Biology, School of Sciences, National and Kapodistrian University of Athens, Panepistimiopolis, Athens 157 01, Greece. Electronic address: gnasi@biol.uoa.gr.
3
Section of Cell Biology and Biophysics, Department of Biology, School of Sciences, National and Kapodistrian University of Athens, Panepistimiopolis, Athens 157 01, Greece. Electronic address: fbaltoumas@biol.uoa.gr.
4
Section of Cell Biology and Biophysics, Department of Biology, School of Sciences, National and Kapodistrian University of Athens, Panepistimiopolis, Athens 157 01, Greece. Electronic address: nlouros@biol.uoa.gr.
5
Department of Pharmacy, University of Patras, Patras 26504, Greece. Electronic address: magafa@upatras.gr.
6
Section of Cell Biology and Biophysics, Department of Biology, School of Sciences, National and Kapodistrian University of Athens, Panepistimiopolis, Athens 157 01, Greece. Electronic address: shamodr@biol.uoa.gr.
7
Section of Cell Biology and Biophysics, Department of Biology, School of Sciences, National and Kapodistrian University of Athens, Panepistimiopolis, Athens 157 01, Greece. Electronic address: veconom@biol.uoa.gr.

Abstract

The Calcitonin-gene related peptide (CGRP) family is a group of peptide hormones, which consists of IAPP, calcitonin, adrenomedullin, intermedin, αCGRP and βCGRP. IAPP and calcitonin have been extensively associated with the formation of amyloid fibrils, causing Type 2 Diabetes and Medullary Thyroid Carcinoma, respectively. In contrast, the potential amyloidogenic properties of αCGRP still remain unexplored, although experimental trials have indicated its presence in deposits, associated with the aforementioned disorders. Therefore, in this work, we investigated the amyloidogenic profile of αCGRP, a 37-residue-long peptide hormone, utilizing both biophysical experimental techniques and Molecular Dynamics simulations. These efforts unravel a novel amyloidogenic member of the CGRP family and provide insights into the mechanism underlying the αCGRP polymerization.

KEYWORDS:

Aggregation assays; CGRP family; Type 2 diabetes; αCGRP; ‘Aggregation-prone’ peptide

PMID:
29501724
DOI:
10.1016/j.jsb.2018.02.008

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