Intrinsically Disordered Proteins

 

Intrinsically disordered proteins (IDPs) are important components in the cellular function and their biological role has been the focus of a growing number of publications. “Liquid-like" granules rich in intrinsically disordered proteins and RNA play key roles in critical cellular functions such as RNA processing and translation. These complexes or RNA and RNA-binding proteins, known as Ribonucleoproteins (RNP), are commonly involved in processing RNA transcripts and mediate cell function in response to stress and other environmental perturbations. The malfunction of these granules has been implicated in numerous diseases, however the mechanistic underpinnings of these disease states is not well understood. Elastin-like polypeptides (ELPs) are a family of lab-designed IDPs which, while not normally found in nature, share many of the same characteristics as natural IDPs including temperature responsiveness and salt/pH sensitivity. Since ELPs are genetically encoded as a sequence of amino acids, they can be fused to various RNA binding proteins and form synthetic IDP-RNA-rich granules. These synthetic granules can be engineered for a variety of synthetic biology applications. For example, one can recreate natural IDP-RNA granules using synthetic IDP-RNA granules to study the mechanistic underpinnings of natural systems and their disease states. From a genetic engineering standpoint, one can use ELPs fused to a protein targeting specific mRNAs to modulate gene expression by sequestering target mRNA using ELPs' temperature-responsive phase separation activity.

Overview of Biomaterial Creation

RNPG graphic

An Ode to IDP's, by Daniel Shapiro:

IDP intrinsically disordered

IDP sway 

IDP protein

IDP binds RNA

 

IDP clump

IDP sequester

IDP hides RNA

Ribosome can’t get ‘er

 

IDP wiggle

IDP repeat 

IDP jiggle 

IDP VPGVGeet 

 

IDP turn gene off 

IDP inhibit

IDP doesn’t work as expected 

IDP a whole clown exhibit 

 

IDP at 20 degrees

IDP soluble

IDP at 37 degrees?

IDP insoluble 

 

IDP is love

IDP is life

IDP doesn’t purify

IDP causes me strife

 

IDP I love you

IDP is for me 

IDP controls gene expression

IDP makes my PhD

Publications

De novo engineering of intracellular condensates using artificial disordered proteins. M. Dzuricky; B.A. Rogers; A. Shahid; P.S. Cremer; A. Chilkoti. (2020).
Complex microparticle architectures from stimuli-responsive intrinsically disordered proteins. S. Roberts; V. Miao; S. Costa; J. Simon; G. Kelly; T. Shah; S. Zauscher; A. Chilkoti. (2020).
Engineered Ribonucleoprotein Granules Inhibit Translation in Protocells. J.R. Simon; S.Ali Eghtesadi; M. Dzuricky; L. You; A. Chilkoti. (2019).
Long circulating genetically encoded intrinsically disordered zwitterionic polypeptides for drug delivery. S. Banskota; P. Yousefpour; N. Kirmani; X. Li; A. Chilkoti. (2019).