Arrestins: structural disorder creates rich functionality.

Abstract:

:Arrestins are soluble relatively small 44-46 kDa proteins that specifically bind hundreds of active phosphorylated GPCRs and dozens of non-receptor partners. There are binding partners that demonstrate preference for each of the known arrestin conformations: free, receptor-bound, and microtubule-bound. Recent evidence suggests that conformational flexibility in every functional state is the defining characteristic of arrestins. Flexibility, or plasticity, of proteins is often described as structural disorder, in contrast to the fixed conformational order observed in high-resolution crystal structures. However, protein-protein interactions often involve highly flexible elements that can assume many distinct conformations upon binding to different partners. Existing evidence suggests that arrestins are no exception to this rule: their flexibility is necessary for functional versatility. The data on arrestins and many other multi-functional proteins indicate that in many cases, "order" might be artificially imposed by highly non-physiological crystallization conditions and/or crystal packing forces. In contrast, conformational flexibility (and its extreme case, intrinsic disorder) is a more natural state of proteins, representing true biological order that underlies their physiologically relevant functions.

journal_name

Protein Cell

journal_title

Protein & cell

authors

Gurevich VV,Gurevich EV,Uversky VN

doi

10.1007/s13238-017-0501-8

subject

Has Abstract

pub_date

2018-12-01 00:00:00

pages

986-1003

issue

12

eissn

1674-800X

issn

1674-8018

pii

10.1007/s13238-017-0501-8

journal_volume

9

pub_type

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