Human cystatin C, an amyloidogenic protein, dimerizes through three-dimensional domain swapping
Janowski, Robert ; Kozak, Maciej ; Jankowska, Elzbieta ; Grzonka, Zbigniew ; Grubb, Anders LU
; Abrahamson, Magnus
LU
and Jaskolski, Mariusz
(2001)
In Nature Structural Biology
8(4).
p.316-320
- Abstract
- The crystal structure of human cystatin C, a protein with amyloidogenic properties and a potent inhibitor of cysteine proteases, reveals how the protein refolds to produce very tight two-fold symmetric dimers while retaining the secondary structure of the monomeric form. The dimerization occurs through three-dimensional domain swapping, a mechanism for forming oligomeric proteins. The reconstituted monomer-like domains are similar to chicken cystatin except for one inhibitory loop that unfolds to form the open interface of the dimer. The structure explains the tendency of human cystatin C to dimerize and suggests a mechanism for its aggregation in the brain arteries of elderly people with amyloid angiopathy. A more severe conformational... (More)
- The crystal structure of human cystatin C, a protein with amyloidogenic properties and a potent inhibitor of cysteine proteases, reveals how the protein refolds to produce very tight two-fold symmetric dimers while retaining the secondary structure of the monomeric form. The dimerization occurs through three-dimensional domain swapping, a mechanism for forming oligomeric proteins. The reconstituted monomer-like domains are similar to chicken cystatin except for one inhibitory loop that unfolds to form the open interface of the dimer. The structure explains the tendency of human cystatin C to dimerize and suggests a mechanism for its aggregation in the brain arteries of elderly people with amyloid angiopathy. A more severe conformational disease is associated with the L68Q mutant of human cystatin C, which causes massive amyloidosis, cerebral hemorrhage and death in young adults. The structure of the three-dimensional domain-swapped dimers shows how the L68Q mutation destabilizes the monomers and makes the partially unfolded intermediate less unstable. Higher aggregates may arise through the three-dimensional domain-swapping mechanism occurring in an open-ended fashion in which partially unfolded molecules are linked into infinite chains. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/131360
- author
- Janowski, Robert
; Kozak, Maciej
; Jankowska, Elzbieta
; Grzonka, Zbigniew
; Grubb, Anders
LU
; Abrahamson, Magnus
LU
and Jaskolski, Mariusz
- organization
- publishing date
- 2001
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Nature Structural Biology
- volume
- 8
- issue
- 4
- pages
- 316 - 320
- publisher
- Nature Publishing Group
- external identifiers
-
- wos:000167811300013
- scopus:0035069135
- pmid:11276250
- ISSN
- 1072-8368
- DOI
- 10.1038/86188
- language
- English
- LU publication?
- yes
- id
- ed769437-600d-4346-9701-32de2da7257a (old id 131360)
- date added to LUP
- 2016-04-01 16:58:06
- date last changed
- 2025-04-04 15:08:27
@article{ed769437-600d-4346-9701-32de2da7257a,
abstract = {{The crystal structure of human cystatin C, a protein with amyloidogenic properties and a potent inhibitor of cysteine proteases, reveals how the protein refolds to produce very tight two-fold symmetric dimers while retaining the secondary structure of the monomeric form. The dimerization occurs through three-dimensional domain swapping, a mechanism for forming oligomeric proteins. The reconstituted monomer-like domains are similar to chicken cystatin except for one inhibitory loop that unfolds to form the open interface of the dimer. The structure explains the tendency of human cystatin C to dimerize and suggests a mechanism for its aggregation in the brain arteries of elderly people with amyloid angiopathy. A more severe conformational disease is associated with the L68Q mutant of human cystatin C, which causes massive amyloidosis, cerebral hemorrhage and death in young adults. The structure of the three-dimensional domain-swapped dimers shows how the L68Q mutation destabilizes the monomers and makes the partially unfolded intermediate less unstable. Higher aggregates may arise through the three-dimensional domain-swapping mechanism occurring in an open-ended fashion in which partially unfolded molecules are linked into infinite chains.}},
author = {{Janowski, Robert and Kozak, Maciej and Jankowska, Elzbieta and Grzonka, Zbigniew and Grubb, Anders and Abrahamson, Magnus and Jaskolski, Mariusz}},
issn = {{1072-8368}},
language = {{eng}},
number = {{4}},
pages = {{316--320}},
publisher = {{Nature Publishing Group}},
series = {{Nature Structural Biology}},
title = {{Human cystatin C, an amyloidogenic protein, dimerizes through three-dimensional domain swapping}},
url = {{https://lup.lub.lu.se/search/files/4833049/624200.pdf}},
doi = {{10.1038/86188}},
volume = {{8}},
year = {{2001}},
}