Checking the conformational stability of cystatin C and its L68Q variant by molecular dynamics studies: Why is the L68Q variant amyloidogenic?
Rodziewicz-Motowidlo, S ; Wahlbom, Maria LU ; Wang, Xin LU ; Lagiewka, J ; Janowski, R ; Jaskolski, M ; Grubb, Anders LU
and Grzonka, Z
(2006)
In Journal of Structural Biology
154(1).
p.68-78
- Abstract
- Human L68Q cystatin C is one of the known human amyloidogenic proteins. In its native state it is a monomer with alpha/beta structure. Experimental evidence suggests that L68Q variant associates into dimeric intermediates and that the dimers subsequently self-assemble to form amyloid deposits and insoluble fibrils. Details of the pathway of L68Q mutant amyloid formation are unclear; however, different experimental approaches with resolutions at molecular level have provided Some clues. Probably, the stability and flexibility of monomeric L68Q variant play essential roles in the early steps of amyloid formation; thus, it is necessary to characterize early conformational changes of L68Q cystatin C monomers. In this paper, we demonstrate the... (More)
- Human L68Q cystatin C is one of the known human amyloidogenic proteins. In its native state it is a monomer with alpha/beta structure. Experimental evidence suggests that L68Q variant associates into dimeric intermediates and that the dimers subsequently self-assemble to form amyloid deposits and insoluble fibrils. Details of the pathway of L68Q mutant amyloid formation are unclear; however, different experimental approaches with resolutions at molecular level have provided Some clues. Probably, the stability and flexibility of monomeric L68Q variant play essential roles in the early steps of amyloid formation; thus, it is necessary to characterize early conformational changes of L68Q cystatin C monomers. In this paper, we demonstrate the possibility that the differences between the monomeric forms of wild-type (wt) cystatin C and its L68Q variant are responsible for higher tendency of the L68Q cystatin C amyloidogenesis. We started our studies with the simulations of wt and L68Q cystatin C monomers. Nanosecond time scale molecular dynamics simulations at 308 K were performed using AMBER7.0 program, The results show that the structure of the L68Q monomer was changed, relative to the wt cystatin C structure. The results support earlier speculation that the L68Q point mutation would easily lead to dimer formation. (c) 2006 Published by Elsevier Inc. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/414383
- author
- Rodziewicz-Motowidlo, S
; Wahlbom, Maria
LU
; Wang, Xin
LU
; Lagiewka, J
; Janowski, R
; Jaskolski, M
; Grubb, Anders
LU
and Grzonka, Z
- organization
- publishing date
- 2006
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- single-point mutation, amyloidosis, conformational change, human cystatin C, molecular dynamics simulation
- in
- Journal of Structural Biology
- volume
- 154
- issue
- 1
- pages
- 68 - 78
- publisher
- Elsevier
- external identifiers
-
- pmid:16446102
- wos:000236561000006
- scopus:33645003090
- ISSN
- 1095-8657
- DOI
- 10.1016/j.jsb.2005.11.015
- language
- English
- LU publication?
- yes
- id
- f471bad6-c110-4629-8782-9cfce2242748 (old id 414383)
- date added to LUP
- 2016-04-01 16:25:33
- date last changed
- 2023-01-04 23:40:16
@article{f471bad6-c110-4629-8782-9cfce2242748,
abstract = {{Human L68Q cystatin C is one of the known human amyloidogenic proteins. In its native state it is a monomer with alpha/beta structure. Experimental evidence suggests that L68Q variant associates into dimeric intermediates and that the dimers subsequently self-assemble to form amyloid deposits and insoluble fibrils. Details of the pathway of L68Q mutant amyloid formation are unclear; however, different experimental approaches with resolutions at molecular level have provided Some clues. Probably, the stability and flexibility of monomeric L68Q variant play essential roles in the early steps of amyloid formation; thus, it is necessary to characterize early conformational changes of L68Q cystatin C monomers. In this paper, we demonstrate the possibility that the differences between the monomeric forms of wild-type (wt) cystatin C and its L68Q variant are responsible for higher tendency of the L68Q cystatin C amyloidogenesis. We started our studies with the simulations of wt and L68Q cystatin C monomers. Nanosecond time scale molecular dynamics simulations at 308 K were performed using AMBER7.0 program, The results show that the structure of the L68Q monomer was changed, relative to the wt cystatin C structure. The results support earlier speculation that the L68Q point mutation would easily lead to dimer formation. (c) 2006 Published by Elsevier Inc.}},
author = {{Rodziewicz-Motowidlo, S and Wahlbom, Maria and Wang, Xin and Lagiewka, J and Janowski, R and Jaskolski, M and Grubb, Anders and Grzonka, Z}},
issn = {{1095-8657}},
keywords = {{single-point mutation; amyloidosis; conformational change; human cystatin C; molecular dynamics simulation}},
language = {{eng}},
number = {{1}},
pages = {{68--78}},
publisher = {{Elsevier}},
series = {{Journal of Structural Biology}},
title = {{Checking the conformational stability of cystatin C and its L68Q variant by molecular dynamics studies: Why is the L68Q variant amyloidogenic?}},
url = {{http://dx.doi.org/10.1016/j.jsb.2005.11.015}},
doi = {{10.1016/j.jsb.2005.11.015}},
volume = {{154}},
year = {{2006}},
}