Link to the University of Pittsburgh Homepage
Link to the University Library System Homepage Link to the Contact Us Form

Amyloid-like fibrils from a domain-swapping protein feature a parallel, in-register conformation without native-like interactions

Li, J and Hoop, CL and Kodali, R and Sivanandam, VN and Van Der Wel, PCA (2011) Amyloid-like fibrils from a domain-swapping protein feature a parallel, in-register conformation without native-like interactions. Journal of Biological Chemistry, 286 (33). 28988 - 28995. ISSN 0021-9258

[img]
Preview
PDF
Available under License : See the attached license file.

Download (2MB) | Preview
[img] Plain Text (licence)
Available under License : See the attached license file.

Download (1kB)

Abstract

The formation of amyloid-like fibrils is characteristic of various diseases, but the underlying mechanism and the factors that determine whether, when, and how proteins form amyloid, remain uncertain. Certain mechanisms have been proposed based on the three-dimensional or runaway domain swapping, inspired by the fact that some proteins show an apparent correlation between the ability to form domain-swapped dimers and a tendency to form fibrillar aggregates. Intramolecular β-sheet contacts present in the monomeric state could constitute intermolecular β-sheets in the dimeric and fibrillar states. One example is an amyloid-forming mutant of the immunoglobulin binding domain B1 of streptococcal protein G, which in its native conformation consists of a four-stranded β-sheet and one α-helix. Under native conditions this mutant adopts a domainswapped dimer, and it also forms amyloid-like fibrils, seemingly in correlation to its domain-swapping ability. We employ magic angle spinning solid-state NMR and other methods to examine key structural features of these fibrils. Our results reveal a highly rigid fibril structure that lacks mobile domains and indicate a parallel in-register β-sheet structure and a general loss of native conformation within the mature fibrils. This observation contrasts with predictions that native structure, and in particular intermolecular β-strand interactions seen in the dimeric state, may be preserved in "domain-swapping" fibrils. We discuss these observations in light of recent work on related amyloidforming proteins that have been argued to follow similar mechanisms and how this may have implications for the role of domain-swapping propensities for amyloid formation. © 2011 by The American Society for Biochemistry and Molecular Biology, Inc.


Share

Citation/Export:
Social Networking:
Share |

Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Li, J
Hoop, CL
Kodali, R
Sivanandam, VN
Van Der Wel, PCApvdwel@pitt.eduPVDWEL0000-0002-5390-3321
Date: 19 August 2011
Date Type: Publication
Journal or Publication Title: Journal of Biological Chemistry
Volume: 286
Number: 33
Page Range: 28988 - 28995
DOI or Unique Handle: 10.1074/jbc.m111.261750
Schools and Programs: School of Medicine > Structural Biology
Refereed: Yes
ISSN: 0021-9258
Date Deposited: 28 Sep 2017 13:54
Last Modified: 02 Feb 2019 16:58
URI: http://d-scholarship.pitt.edu/id/eprint/33222

Metrics

Monthly Views for the past 3 years

Plum Analytics

Altmetric.com


Actions (login required)

View Item View Item