---
OA_place: repository
OA_type: green
_id: '17331'
abstract:
- lang: eng
text: Amyloidosis are a group of diseases in which soluble proteins aggregate and
deposit in fibrillar conformation extracellularly in tissues. The effectiveness
of therapeutic strategies depends on the specific protein involved, being crucial
to accurately determine its nature. Moreover, following the diagnosis, the search
for the mutation within relatives allows the clinical advice. Here we report the
precise diagnosis and explored the possible reasons of the structural pathogenicity
for a renal amyloidosis related to a fibrinogen Aα-chain variant. Whole-exome
sequencing and GATK calling pipeline were leveraged to characterize the protein
variant present in a patient with kidney failure. Bioinformatics strategies were
applied to suggest potential explanations of the variants aggregation. Our pipeline
allowed the identification of a single-point variant of fibrinogen Aα-chain, which
opened the possibility of curative transplantation. In silico structural analysis
suggested that the pathogenicity of the variant may be attributed to a heightened
susceptibility to yield a peptide prone to deposit as an oligomer with a β-sheet
structure. Exploiting the comprehensive coverage of whole-genome sequencing, we
managed to fill a vacant stage in the diagnosis of hereditary amyloidosis and
to stimulate the advancement in biomedicine.
acknowledgement: The authors acknowledge Rosana del Cid for her help with English
corrections, Mario Ramos for the figure editions, and Gabriela Finarelli for technical
assistance. S.A. Rosú, N.A. Ramella, and M.A. Tricerri acknowledge support from
Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) (Grant PIP
11220200102381), Agencia Nacional de Promoción Científica y Tecnológica (PICT 2019-03592),
Universidad Nacional de La Plata (UNLP) (Grants M234 and PPID M014), and Fundación
Florencio Fiorini. The authors warmly thank M.P. for her willingness to conduct
these studies.
article_processing_charge: No
article_type: original
author:
- first_name: Elizabeth R
full_name: Cattaneo, Elizabeth R
last_name: Cattaneo
- first_name: Romina A
full_name: Gisonno, Romina A
id: a9e08d76-6a98-11ec-8f7b-c777fe5ca519
last_name: Gisonno
- first_name: Martín C
full_name: Abba, Martín C
last_name: Abba
- first_name: Marianela
full_name: Santana, Marianela
last_name: Santana
- first_name: Silvana A
full_name: Rosú, Silvana A
last_name: Rosú
- first_name: Elsa
full_name: Nucifora, Elsa
last_name: Nucifora
- first_name: María A
full_name: Aguirre, María A
last_name: Aguirre
- first_name: María C
full_name: Giordani, María C
last_name: Giordani
- first_name: M. Alejandra
full_name: Tricerri, M. Alejandra
last_name: Tricerri
- first_name: Nahuel A
full_name: Ramella, Nahuel A
last_name: Ramella
citation:
ama: 'Cattaneo ER, Gisonno RA, Abba MC, et al. Hereditary amyloidosis: Insights
into a fibrinogen A variant protein. Proteins: Structure, Function and Bioinformatics.
2024;92(12):1366-1374. doi:10.1002/prot.26732'
apa: 'Cattaneo, E. R., Gisonno, R. A., Abba, M. C., Santana, M., Rosú, S. A., Nucifora,
E., … Ramella, N. A. (2024). Hereditary amyloidosis: Insights into a fibrinogen
A variant protein. Proteins: Structure, Function and Bioinformatics. Wiley.
https://doi.org/10.1002/prot.26732'
chicago: 'Cattaneo, Elizabeth R, Romina A Gisonno, Martín C Abba, Marianela Santana,
Silvana A Rosú, Elsa Nucifora, María A Aguirre, María C Giordani, M. Alejandra
Tricerri, and Nahuel A Ramella. “Hereditary Amyloidosis: Insights into a Fibrinogen
A Variant Protein.” Proteins: Structure, Function and Bioinformatics. Wiley,
2024. https://doi.org/10.1002/prot.26732.'
ieee: 'E. R. Cattaneo et al., “Hereditary amyloidosis: Insights into a fibrinogen
A variant protein,” Proteins: Structure, Function and Bioinformatics, vol.
92, no. 12. Wiley, pp. 1366–1374, 2024.'
ista: 'Cattaneo ER, Gisonno RA, Abba MC, Santana M, Rosú SA, Nucifora E, Aguirre
MA, Giordani MC, Tricerri MA, Ramella NA. 2024. Hereditary amyloidosis: Insights
into a fibrinogen A variant protein. Proteins: Structure, Function and Bioinformatics.
92(12), 1366–1374.'
mla: 'Cattaneo, Elizabeth R., et al. “Hereditary Amyloidosis: Insights into a Fibrinogen
A Variant Protein.” Proteins: Structure, Function and Bioinformatics, vol.
92, no. 12, Wiley, 2024, pp. 1366–74, doi:10.1002/prot.26732.'
short: 'E.R. Cattaneo, R.A. Gisonno, M.C. Abba, M. Santana, S.A. Rosú, E. Nucifora,
M.A. Aguirre, M.C. Giordani, M.A. Tricerri, N.A. Ramella, Proteins: Structure,
Function and Bioinformatics 92 (2024) 1366–1374.'
date_created: 2024-07-28T22:01:10Z
date_published: 2024-12-01T00:00:00Z
date_updated: 2025-09-08T08:33:53Z
day: '01'
department:
- _id: GaNo
doi: 10.1002/prot.26732
external_id:
isi:
- '001272128100001'
pmid:
- '39031927'
intvolume: ' 92'
isi: 1
issue: '12'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.22541/au.171804763.37967262/v1
month: '12'
oa: 1
oa_version: Preprint
page: 1366-1374
pmid: 1
publication: 'Proteins: Structure, Function and Bioinformatics'
publication_identifier:
eissn:
- 1097-0134
issn:
- 0887-3585
publication_status: published
publisher: Wiley
quality_controlled: '1'
scopus_import: '1'
status: public
title: 'Hereditary amyloidosis: Insights into a fibrinogen A variant protein'
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 92
year: '2024'
...
---
_id: '15268'
abstract:
- lang: eng
text: Apolipoprotein A‐I (apoA‐I) has a key function in the reverse cholesterol
transport. However, aggregation of apoA‐I single point mutants can lead to hereditary
amyloid pathology. Although several studies have tackled the biophysical and structural
consequences introduced by these mutations, there is little information addressing
the relationship between the evolutionary and structural features that contribute
to the amyloid behavior of apoA‐I. We combined evolutionary studies, in silico
mutagenesis and molecular dynamics (MD) simulations to provide a comprehensive
analysis of the conservation and pathogenic role of the aggregation‐prone regions
(APRs) present in apoA‐I. Sequence analysis demonstrated that among the four amyloidogenic
regions described for human apoA‐I, only two (APR1 and APR4) are evolutionary
conserved across different species of Sarcopterygii. Moreover, stability analysis
carried out with the FoldX engine showed that APR1 contributes to the marginal
stability of apoA‐I. Structural properties of full‐length apoA‐I models suggest
that aggregation is avoided by placing APRs into highly packed and rigid portions
of its native fold. Compared to silent variants extracted from the gnomAD database,
the thermodynamic and pathogenic impact of amyloid mutations showed evidence of
a higher destabilizing effect. MD simulations of the amyloid variant G26R evidenced
the partial unfolding of the alpha‐helix bundle with the concomitant exposure
of APR1 to the solvent, suggesting an insight into the early steps involved in
its aggregation. Our findings highlight APR1 as a relevant component for apoA‐I
structural integrity and emphasize a destabilizing effect of amyloid variants
that leads to the exposure of this region.
article_processing_charge: No
article_type: original
author:
- first_name: Romina A.
full_name: Gisonno, Romina A.
last_name: Gisonno
- first_name: Tomas
full_name: Masson, Tomas
id: 93ac43e8-8599-11eb-9b86-f6efb0a4c207
last_name: Masson
orcid: 0000-0002-2634-6283
- first_name: Nahuel A.
full_name: Ramella, Nahuel A.
last_name: Ramella
- first_name: Exequiel E.
full_name: Barrera, Exequiel E.
last_name: Barrera
- first_name: Víctor
full_name: Romanowski, Víctor
last_name: Romanowski
- first_name: M. Alejandra
full_name: Tricerri, M. Alejandra
last_name: Tricerri
citation:
ama: 'Gisonno RA, Masson T, Ramella NA, Barrera EE, Romanowski V, Tricerri MA. Evolutionary
and structural constraints influencing apolipoprotein A‐I amyloid behavior. Proteins:
Structure, Function, and Bioinformatics. 2022;90(1):258-269. doi:10.1002/prot.26217'
apa: 'Gisonno, R. A., Masson, T., Ramella, N. A., Barrera, E. E., Romanowski, V.,
& Tricerri, M. A. (2022). Evolutionary and structural constraints influencing
apolipoprotein A‐I amyloid behavior. Proteins: Structure, Function, and Bioinformatics.
Wiley. https://doi.org/10.1002/prot.26217'
chicago: 'Gisonno, Romina A., Tomas Masson, Nahuel A. Ramella, Exequiel E. Barrera,
Víctor Romanowski, and M. Alejandra Tricerri. “Evolutionary and Structural Constraints
Influencing Apolipoprotein A‐I Amyloid Behavior.” Proteins: Structure, Function,
and Bioinformatics. Wiley, 2022. https://doi.org/10.1002/prot.26217.'
ieee: 'R. A. Gisonno, T. Masson, N. A. Ramella, E. E. Barrera, V. Romanowski, and
M. A. Tricerri, “Evolutionary and structural constraints influencing apolipoprotein
A‐I amyloid behavior,” Proteins: Structure, Function, and Bioinformatics,
vol. 90, no. 1. Wiley, pp. 258–269, 2022.'
ista: 'Gisonno RA, Masson T, Ramella NA, Barrera EE, Romanowski V, Tricerri MA.
2022. Evolutionary and structural constraints influencing apolipoprotein A‐I amyloid
behavior. Proteins: Structure, Function, and Bioinformatics. 90(1), 258–269.'
mla: 'Gisonno, Romina A., et al. “Evolutionary and Structural Constraints Influencing
Apolipoprotein A‐I Amyloid Behavior.” Proteins: Structure, Function, and Bioinformatics,
vol. 90, no. 1, Wiley, 2022, pp. 258–69, doi:10.1002/prot.26217.'
short: 'R.A. Gisonno, T. Masson, N.A. Ramella, E.E. Barrera, V. Romanowski, M.A.
Tricerri, Proteins: Structure, Function, and Bioinformatics 90 (2022) 258–269.'
corr_author: '1'
date_created: 2024-04-03T07:49:53Z
date_published: 2022-01-01T00:00:00Z
date_updated: 2024-10-09T21:08:44Z
day: '01'
department:
- _id: MaJö
doi: 10.1002/prot.26217
external_id:
pmid:
- '34414600'
intvolume: ' 90'
issue: '1'
keyword:
- Molecular Biology
- Biochemistry
- Structural Biology
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.1101/2020.09.18.304337
month: '01'
oa: 1
oa_version: Preprint
page: 258-269
pmid: 1
publication: 'Proteins: Structure, Function, and Bioinformatics'
publication_identifier:
eissn:
- 1097-0134
issn:
- 0887-3585
publication_status: published
publisher: Wiley
quality_controlled: '1'
status: public
title: Evolutionary and structural constraints influencing apolipoprotein A‐I amyloid
behavior
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 90
year: '2022'
...
---
_id: '4011'
abstract:
- lang: eng
text: The size and shape of macromolecules such as proteins and nucleic acids play
an important role in their functions. Prior efforts to quantify these properties
have been based on various discretization or tessellation procedures involving
analytical or numerical computations. In this article, we present an analytically
exact method for computing the metric properties of macromolecules based on the
alpha shape theory. This method uses the duality between alpha complex and the
weighted Voronoi decomposition of a molecule. We describe the intuitive ideas
and concepts behind the alpha shape theory and the algorithm for computing areas
and volumes of macromolecules. We apply our method to compute areas and volumes
of a number of protein systems. We also discuss several difficulties commonly
encountered in molecular shape computations and outline methods to overcome these
problems. (C) 1998 Wiley-Liss, Inc.
acknowledgement: We thank Michael Facello for the torus area formula and suggestion
regarding computation of MS model from SA model. We thank Nataraj Akkiraju, Patrick
Moran, and Marcus Wagner for interesting discussionson the topic of this article
and for help in the generationof two- and three-dimensional illustrations. We thank
NSF Meta Center Allocation for providing computational resources. The software
VOLBL is available at:http://alpha.ncsa.uiuc.edu/alpha.
article_processing_charge: No
article_type: original
author:
- first_name: Jie
full_name: Liang, Jie
last_name: Liang
- first_name: Herbert
full_name: Edelsbrunner, Herbert
id: 3FB178DA-F248-11E8-B48F-1D18A9856A87
last_name: Edelsbrunner
orcid: 0000-0002-9823-6833
- first_name: Ping
full_name: Fu, Ping
last_name: Fu
- first_name: Pamidighantam
full_name: Sudhakar, Pamidighantam
last_name: Sudhakar
- first_name: Shankar
full_name: Subramaniam, Shankar
last_name: Subramaniam
citation:
ama: 'Liang J, Edelsbrunner H, Fu P, Sudhakar P, Subramaniam S. Analytical shape
computation of macromolecules: I. molecular area and volume through alpha shape.
Proteins: Structure, Function and Bioinformatics. 1998;33(1):1-17. doi:10.1002/(SICI)1097-0134(19981001)33:1<1::AID-PROT1>3.0.CO;2-O'
apa: 'Liang, J., Edelsbrunner, H., Fu, P., Sudhakar, P., & Subramaniam, S. (1998).
Analytical shape computation of macromolecules: I. molecular area and volume through
alpha shape. Proteins: Structure, Function and Bioinformatics. Wiley-Blackwell.
https://doi.org/10.1002/(SICI)1097-0134(19981001)33:1<1::AID-PROT1>3.0.CO;2-O'
chicago: 'Liang, Jie, Herbert Edelsbrunner, Ping Fu, Pamidighantam Sudhakar, and
Shankar Subramaniam. “Analytical Shape Computation of Macromolecules: I. Molecular
Area and Volume through Alpha Shape.” Proteins: Structure, Function and Bioinformatics.
Wiley-Blackwell, 1998. https://doi.org/10.1002/(SICI)1097-0134(19981001)33:1<1::AID-PROT1>3.0.CO;2-O.'
ieee: 'J. Liang, H. Edelsbrunner, P. Fu, P. Sudhakar, and S. Subramaniam, “Analytical
shape computation of macromolecules: I. molecular area and volume through alpha
shape,” Proteins: Structure, Function and Bioinformatics, vol. 33, no.
1. Wiley-Blackwell, pp. 1–17, 1998.'
ista: 'Liang J, Edelsbrunner H, Fu P, Sudhakar P, Subramaniam S. 1998. Analytical
shape computation of macromolecules: I. molecular area and volume through alpha
shape. Proteins: Structure, Function and Bioinformatics. 33(1), 1–17.'
mla: 'Liang, Jie, et al. “Analytical Shape Computation of Macromolecules: I. Molecular
Area and Volume through Alpha Shape.” Proteins: Structure, Function and Bioinformatics,
vol. 33, no. 1, Wiley-Blackwell, 1998, pp. 1–17, doi:10.1002/(SICI)1097-0134(19981001)33:1<1::AID-PROT1>3.0.CO;2-O.'
short: 'J. Liang, H. Edelsbrunner, P. Fu, P. Sudhakar, S. Subramaniam, Proteins:
Structure, Function and Bioinformatics 33 (1998) 1–17.'
date_created: 2018-12-11T12:06:25Z
date_published: 1998-10-01T00:00:00Z
date_updated: 2022-08-25T13:32:59Z
day: '01'
doi: 10.1002/(SICI)1097-0134(19981001)33:1<1::AID-PROT1>3.0.CO;2-O
extern: '1'
intvolume: ' 33'
issue: '1'
language:
- iso: eng
month: '10'
oa_version: None
page: 1 - 17
publication: 'Proteins: Structure, Function and Bioinformatics'
publication_identifier:
issn:
- 0887-3585
publication_status: published
publisher: Wiley-Blackwell
publist_id: '2112'
quality_controlled: '1'
scopus_import: '1'
status: public
title: 'Analytical shape computation of macromolecules: I. molecular area and volume
through alpha shape'
type: journal_article
user_id: ea97e931-d5af-11eb-85d4-e6957dddbf17
volume: 33
year: '1998'
...
---
_id: '4012'
abstract:
- lang: eng
text: The structures of proteins are well-packed, yet they contain numerous cavities
which play key roles in accommodating small molecules, or enabling conformational
changes. From high-resolution structures it is possible to identify these cavities.
We have developed a precise algorithm based on alpha shapes for measuring space-filling-based
molecular models (such as van der Waals, solvent accessible, and molecular surface
descriptions). We applied this method for accurate computation of the surface
area and volume of cavities in several proteins. In addition, all of the atoms/residues
Lining the cavities are identified, We use this method to study the structure
and the stability of proteins, as well as to locate cavities that could contain
structural water molecules in the proton transport pathway in the membrane protein
bacteriorhodopsin.
acknowledgement: The software for constructing weighted Delaunay complexes and the
alpha shape filters was written by Ernst Mücke and Michael Facello. We thank them
forcreating reliable and robust software so that wecan build on their results. The
authors thank NSF Meta Center Allocation for providing computational resources.
The software VOLBL is part of the standard distribution of the alpha shapes software,
andis available at http://alpha.ncsa.uiuc.edu/alpha.
article_processing_charge: No
article_type: original
author:
- first_name: Jie
full_name: Liang, Jie
last_name: Liang
- first_name: Herbert
full_name: Edelsbrunner, Herbert
id: 3FB178DA-F248-11E8-B48F-1D18A9856A87
last_name: Edelsbrunner
orcid: 0000-0002-9823-6833
- first_name: Ping
full_name: Fu, Ping
last_name: Fu
- first_name: Pamidighantam
full_name: Sudhakar, Pamidighantam
last_name: Sudhakar
- first_name: Shankar
full_name: Subramaniam, Shankar
last_name: Subramaniam
citation:
ama: 'Liang J, Edelsbrunner H, Fu P, Sudhakar P, Subramaniam S. Analytical shape
computation of macromolecules: II. Inaccessible cavities in proteins. Proteins:
Structure, Function and Bioinformatics. 1998;33(1):18-29. doi:10.1002/(SICI)1097-0134(19981001)33:1<18::AID-PROT2>3.0.CO;2-H'
apa: 'Liang, J., Edelsbrunner, H., Fu, P., Sudhakar, P., & Subramaniam, S. (1998).
Analytical shape computation of macromolecules: II. Inaccessible cavities in proteins.
Proteins: Structure, Function and Bioinformatics. Wiley-Blackwell. https://doi.org/10.1002/(SICI)1097-0134(19981001)33:1<18::AID-PROT2>3.0.CO;2-H'
chicago: 'Liang, Jie, Herbert Edelsbrunner, Ping Fu, Pamidighantam Sudhakar, and
Shankar Subramaniam. “Analytical Shape Computation of Macromolecules: II. Inaccessible
Cavities in Proteins.” Proteins: Structure, Function and Bioinformatics.
Wiley-Blackwell, 1998. https://doi.org/10.1002/(SICI)1097-0134(19981001)33:1<18::AID-PROT2>3.0.CO;2-H.'
ieee: 'J. Liang, H. Edelsbrunner, P. Fu, P. Sudhakar, and S. Subramaniam, “Analytical
shape computation of macromolecules: II. Inaccessible cavities in proteins,” Proteins:
Structure, Function and Bioinformatics, vol. 33, no. 1. Wiley-Blackwell, pp.
18–29, 1998.'
ista: 'Liang J, Edelsbrunner H, Fu P, Sudhakar P, Subramaniam S. 1998. Analytical
shape computation of macromolecules: II. Inaccessible cavities in proteins. Proteins:
Structure, Function and Bioinformatics. 33(1), 18–29.'
mla: 'Liang, Jie, et al. “Analytical Shape Computation of Macromolecules: II. Inaccessible
Cavities in Proteins.” Proteins: Structure, Function and Bioinformatics,
vol. 33, no. 1, Wiley-Blackwell, 1998, pp. 18–29, doi:10.1002/(SICI)1097-0134(19981001)33:1<18::AID-PROT2>3.0.CO;2-H.'
short: 'J. Liang, H. Edelsbrunner, P. Fu, P. Sudhakar, S. Subramaniam, Proteins:
Structure, Function and Bioinformatics 33 (1998) 18–29.'
date_created: 2018-12-11T12:06:26Z
date_published: 1998-10-01T00:00:00Z
date_updated: 2022-08-25T13:35:41Z
day: '01'
doi: 10.1002/(SICI)1097-0134(19981001)33:1<18::AID-PROT2>3.0.CO;2-H
extern: '1'
intvolume: ' 33'
issue: '1'
language:
- iso: eng
month: '10'
oa_version: None
page: 18 - 29
publication: 'Proteins: Structure, Function and Bioinformatics'
publication_identifier:
issn:
- 0887-3585
publication_status: published
publisher: Wiley-Blackwell
publist_id: '2113'
quality_controlled: '1'
scopus_import: '1'
status: public
title: 'Analytical shape computation of macromolecules: II. Inaccessible cavities
in proteins'
type: journal_article
user_id: ea97e931-d5af-11eb-85d4-e6957dddbf17
volume: 33
year: '1998'
...