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The Physiological Molecular Shape of Spectrin: A Compact Supercoil Resembling a Chinese Finger Trap

Brown, JW and Bullitt, E and Sriswasdi, S and Harper, S and Speicher, DW and McKnight, CJ (2015) The Physiological Molecular Shape of Spectrin: A Compact Supercoil Resembling a Chinese Finger Trap. PLoS Computational Biology, 11 (6). ISSN 1553-734X

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Abstract

© 2015 Brown et al. The primary, secondary, and tertiary structures of spectrin are reasonably well defined, but the structural basis for the known dramatic molecular shape change, whereby the molecular length can increase three-fold, is not understood. In this study, we combine previously reported biochemical and high-resolution crystallographic data with structural mass spectroscopy and electron microscopic data to derive a detailed, experimentally-supported quaternary structure of the spectrin heterotetramer. In addition to explaining spectrin’s physiological resting length of ~55-65 nm, our model provides a mechanism by which spectrin is able to undergo a seamless three-fold extension while remaining a linear filament, an experimentally observed property. According to the proposed model, spectrin’s quaternary structure and mechanism of extension is similar to a Chinese Finger Trap: at shorter molecular lengths spectrin is a hollow cylinder that extends by increasing the pitch of each spectrin repeat, which decreases the internal diameter. We validated our model with electron microscopy, which demonstrated that, as predicted, spectrin is hollow at its biological resting length of ~55-65 nm. The model is further supported by zero-length chemical crosslink data indicative of an approximately 90 degree bend between adjacent spectrin repeats. The domain-domain interactions in our model are entirely consistent with those present in the prototypical linear antiparallel heterotetramer as well as recently reported inter-strand chemical crosslinks. The model is consistent with all known physical properties of spectrin, and upon full extension our Chinese Finger Trap Model reduces to the ~180-200 nm molecular model currently in common use.

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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Brown, JW
Bullitt, E
Sriswasdi, S
Harper, S
Speicher, DW
McKnight, CJ
Date: 11 June 2015
Date Type: Publication
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Journal or Publication Title: PLoS Computational Biology
Volume: 11
Number: 6
DOI or Unique Handle: 10.1371/journal.pcbi.1004302
Institution: University of Pittsburgh
Refereed: Yes
ISSN: 1553-734X
Date Deposited: 23 Aug 2016 13:42
Last Modified: 20 Dec 2018 00:55
URI: http://d-scholarship.pitt.edu/id/eprint/28514

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