Multivalent IDP assemblies: Unique properties of LC8‐associated, IDP duplex scaffolds

Abstract

A wide variety of subcellular complexes are composed of one or more intrinsically disordered proteins (IDPs) that are multivalent, flexible, and characterized by dynamic binding of diverse partner proteins. These multivalent IDP assemblies, of broad functional diversity, are classified here into five categories distinguished by the number of IDP chains and the arrangement of partner proteins in the functional complex. Examples of each category are summarized in the context of the exceptional molecular and biological properties of IDPs. One type – IDP duplex scaffolds – is considered in detail. Its unique features include parallel alignment of two IDP chains, formation of new self-associated domains, enhanced affinity for additional bivalent ligands, and ubiquitous binding of the hub protein LC8. For two IDP duplex scaffolds, dynein intermediate chain IC and nucleoporin Nup159, these duplex features, together with the inherent flexibility of IDPs, are central to their assembly and function. A new type of IDP-LC8 interaction, distributed binding of LC8 among multiple IDP recognition sites, is described for Nup159 assembly.

High‐affinity heterotetramer formation between the large myelin‐associated glycoprotein and the dynein light chainDYNLL1

“…These data are in agreement with the critical role of the dynein complex in neurodevelopment and myelination, as recently shown by analysing both PNS and CNS of zebrafish carrying a mutation in the gene encoding dynein heavy chain (dync1 h1) (Langworthy and Appel 2012;Yang et al 2015). On the other hand, DYNLL1 is recognized as having independent functions outside the dynein complex, which often relate to interactions with, and dimerization of, IDPs (Barbar 2008;Clark et al 2015). Hence, the L-MAG-DYNLL1 interaction may also be distinct from any larger dynein complex.…”

“…Apart from being a subunit in the dynein complex, DYNLL1 is known to be a mediator of intrinsically disordered protein (IDP) dimerization (Clark et al . ). The frequency of DYNLL1‐positive clones is suggestive of a high‐affinity interaction, although the high hit rate also reflects the fact that the DYNLL1 open reading frame is small.…”

“…All 14 plasmids independently selected from the library represented the entire open reading frame of DYNLL1, a subunit of the dynein complex that mediates dimerization of various target proteins and vesicular trafficking (Barbar 2008;Rapali et al 2011b). Apart from being a subunit in the dynein complex, DYNLL1 is known to be a mediator of intrinsically disordered protein (IDP) dimerization (Clark et al 2015). The frequency of DYNLL1-positive clones is suggestive of a high-affinity interaction, although the high hit Detection of complex formation in size exclusion chromatography.…”

“…On the other hand, DYNLL1 is recognized as having independent functions outside the dynein complex, which often relate to interactions with, and dimerization of, IDPs (Barbar ; Clark et al . ). Hence, the L‐MAG‐DYNLL1 interaction may also be distinct from any larger dynein complex.…”

“…DYNLL1 is known for its ability to promote dimerization of IDPs (Clark et al . ). The L‐MAGct is an IDP, as predicted and shown here, and gets dimerized through DYNLL1.…”