Design and Engineering of Biostasis Proteins
Abstract
Intrinsically disordered proteins with protective properties exhibit amphipathic helical repeats In our initial library of ~100 IDPs derived from extremotolerant organisms, we observed through sequence analysis that most of these proteins exhibit a repeated helix-linker-helix motif, in which the helical regions have notable amphipathic character with polar residues enriched on one side and non-polar residues enriched on the opposing side. We hypothesized that this motif indicated a sticker-spacer structure permitting self-interaction that could lead to formation of higher-order structures from these IDPs. This motivated our design of synthetic variants isolating these repeat regions, mutating the helices to test specific hypotheses regarding potential interactions, identifying proteins with similar motifs in the human proteome, and developing completely synthetic sequences with the same motif that can self-interact. Throughout the course of this project, we assembled a gene expression construct library of ~500 of these naturally-occurring and designed sequences to be tested in functional assays as candidate biostasis proteins.
Document Details
- Document Type
- Technical Report
- Publication Date
- Feb 28, 2022
- Accession Number
- AD1210734
Entities
People
- Pamela Silver
Organizations
- Harvard Medical School