5KNZ

Human Islet Amyloid Polypeptide Segment 19-SGNNFGAILSS-29 with Early Onset S20G Mutation Determined by MicroED

Summary for 5KNZ

• Entry DOI: 10.2210/pdb5knz/pdb
• Related: 5KO0
• EMDB information: 8272 8273
• Descriptor: hIAPP(residues 19-29)S20G (2 entities in total)
• Functional Keywords: amyloid, islet amyloid polypeptide, type ii diabetes, toxic spine, microed, protein fibril
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 1066.13

Authors

Krotee, P.A.L.,Rodriguez, J.A.,Sawaya, M.R.,Cascio, D.,Shi, D.,Nannenga, B.L.,Hattne, J.,Reyes, F.E.,Gonen, T.,Eisenberg, D.S. (deposition date: 2016-06-28, release date: 2016-12-21, Last modification date: 2024-03-06)

Primary citation

Krotee, P.,Rodriguez, J.A.,Sawaya, M.R.,Cascio, D.,Reyes, F.E.,Shi, D.,Hattne, J.,Nannenga, B.L.,Oskarsson, M.E.,Philipp, S.,Griner, S.,Jiang, L.,Glabe, C.G.,Westermark, G.T.,Gonen, T.,Eisenberg, D.S.
Atomic structures of fibrillar segments of hIAPP suggest tightly mated beta-sheets are important for cytotoxicity.
Elife, 6:-, 2017

PubMed Abstract: hIAPP fibrils are associated with Type-II Diabetes, but the link of hIAPP structure to islet cell death remains elusive. Here we observe that hIAPP fibrils are cytotoxic to cultured pancreatic β-cells, leading us to determine the structure and cytotoxicity of protein segments composing the amyloid spine of hIAPP. Using the cryoEM method MicroED, we discover that one segment, 19-29 S20G, forms pairs of β-sheets mated by a dry interface that share structural features with and are similarly cytotoxic to full-length hIAPP fibrils. In contrast, a second segment, 15-25 WT, forms non-toxic labile β-sheets. These segments possess different structures and cytotoxic effects, however, both can seed full-length hIAPP, and cause hIAPP to take on the cytotoxic and structural features of that segment. These results suggest that protein segment structures represent polymorphs of their parent protein and that segment 19-29 S20G may serve as a model for the toxic spine of hIAPP.

PubMed: 28045370
DOI: 10.7554/eLife.19273

Experimental method

ELECTRON CRYSTALLOGRAPHY (1.9 Å)