Fusion of two unrelated protein domains in a chimera protein
and its 3D prediction: Justification of the x-ray reference
structures as a prediction benchmark

J 2022

Fusion of two unrelated protein domains in a chimera protein and its 3D prediction: Justification of the x-ray reference structures as a prediction benchmark

VYMETAL, Jiri; Katerina MERTOVA; Kristyna BOUSOVA; Josef SULC; Konstantinos TRIPSIANES et al.

Základní údaje

Originální název

Fusion of two unrelated protein domains in a chimera protein and its 3D prediction: Justification of the x-ray reference structures as a prediction benchmark

Autoři

VYMETAL, Jiri; Katerina MERTOVA; Kristyna BOUSOVA; Josef SULC; Konstantinos TRIPSIANES a Jiri VONDRASEK

Vydání

Proteins: Structure, Function, and Bioinformatics, 2022, 0887-3585

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10608 Biochemistry and molecular biology

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 2.900

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14740/22:00128476

Organizační jednotka

Středoevropský technologický institut

Klíčová slova anglicky

3D structure prediction; fusion proteins; molecular simulations; x-ray crystallography

Štítky

rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 31. 10. 2024 09:21, Ing. Monika Szurmanová, Ph.D.

Anotace

V originále

Proteins are naturally formed by domains edging their functional and structural properties. A domain out of the context of an entire protein can retain its structure and to some extent also function on its own. These properties rationalize construction of artificial fusion multidomain proteins with unique combination of various functions. Information on the specific functional and structural characteristics of individual domains in the context of new artificial fusion proteins is inevitably encoded in sequential order of composing domains defining their mutual spatial positions. So the challenges in designing new proteins with new domain combinations lie dominantly in structure/function prediction and its context dependency. Despite the enormous body of publications on artificial fusion proteins, the task of their structure/function prediction is complex and nontrivial. The degree of spatial freedom facilitated by a linker between domains and their mutual orientation driven by noncovalent interactions is beyond a simple and straightforward methodology to predict their structure with reasonable accuracy. In the presented manuscript, we tested methodology using available modeling tools and computational methods. We show that the process and methodology of such prediction are not straightforward and must be done with care even when recently introduced AlphaFold II is used. We also addressed a question of benchmarking standards for prediction of multidomain protein structures-x-ray or Nuclear Magnetic Resonance experiments. On the study of six two-domain protein chimeras as well as their composing domains and their x-ray structures selected from PDB, we conclude that the major obstacle for justified prediction is inappropriate sampling of the conformational space by the explored methods. On the other hands, we can still address particular steps of the methodology and improve the process of chimera proteins prediction.

Návaznosti

GA19-03488S, projekt VaV

Název: Ovládání na dálku: Alosterická kontrola selektivity PDZ3 domény ze ZO-1 proteinu v chimerických fúzních konstruktech

Investor: Grantová agentura ČR, Working from distance: engineering allosteric control on PDZ3 domain selectivity from ZO-1 protein through chimera domain fusion

LM2018140, projekt VaV

Název: e-Infrastruktura CZ (Akronym: e-INFRA CZ)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, e-Infrastruktura CZ

LQ1601, projekt VaV

Název: CEITEC 2020 (Akronym: CEITEC2020)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, CEITEC 2020

90131, velká výzkumná infrastruktura

Název: ELIXIR-CZ II

Citovat

VYMETAL, Jiri; Katerina MERTOVA; Kristyna BOUSOVA; Josef SULC; Konstantinos TRIPSIANES a Jiri VONDRASEK. Fusion of two unrelated protein domains in a chimera protein and its 3D prediction: Justification of the x-ray reference structures as a prediction benchmark. Proteins: Structure, Function, and Bioinformatics. 2022, roč. 90, č. 12, s. 2067-2079. ISSN 0887-3585. Dostupné z: https://doi.org/10.1002/prot.26398.

@article{2251930,
   author = {Vymetal, Jiri and Mertova, Katerina and Bousova, Kristyna and Sulc, Josef and Tripsianes, Konstantinos and Vondrasek, Jiri},
   article_number = {12},
   doi = {https://doi.org/10.1002/prot.26398},
   keywords = {3D structure prediction; fusion proteins; molecular simulations; x-ray crystallography},
   language = {eng},
   issn = {0887-3585},
   journal = {Proteins: Structure, Function, and Bioinformatics},
   title = {Fusion of two unrelated protein domains in a chimera protein and its 3D prediction: Justification of the x-ray reference structures as a prediction benchmark},
   url = {https://onlinelibrary.wiley.com/doi/10.1002/prot.26398},
   volume = {90},
   year = {2022}
}

TY  - JOUR
ID  - 2251930
AU  - Vymetal, Jiri - Mertova, Katerina - Bousova, Kristyna - Sulc, Josef - Tripsianes, Konstantinos - Vondrasek, Jiri
PY  - 2022
TI  - Fusion of two unrelated protein domains in a chimera protein and its 3D prediction: Justification of the x-ray reference structures as a prediction benchmark
JF  - Proteins: Structure, Function, and Bioinformatics
VL  - 90
IS  - 12
SP  - 2067-2079
EP  - 2067-2079
SN  - 08873585
KW  - 3D structure prediction
KW  - fusion proteins
KW  - molecular simulations
KW  - x-ray crystallography
UR  - https://onlinelibrary.wiley.com/doi/10.1002/prot.26398
N2  - Proteins are naturally formed by domains edging their functional and structural properties. A domain out of the context of an entire protein can retain its structure and to some extent also function on its own. These properties rationalize construction of artificial fusion multidomain proteins with unique combination of various functions. Information on the specific functional and structural characteristics of individual domains in the context of new artificial fusion proteins is inevitably encoded in sequential order of composing domains defining their mutual spatial positions. So the challenges in designing new proteins with new domain combinations lie dominantly in structure/function prediction and its context dependency. Despite the enormous body of publications on artificial fusion proteins, the task of their structure/function prediction is complex and nontrivial. The degree of spatial freedom facilitated by a linker between domains and their mutual orientation driven by noncovalent interactions is beyond a simple and straightforward methodology to predict their structure with reasonable accuracy. In the presented manuscript, we tested methodology using available modeling tools and computational methods. We show that the process and methodology of such prediction are not straightforward and must be done with care even when recently introduced AlphaFold II is used. We also addressed a question of benchmarking standards for prediction of multidomain protein structures-x-ray or Nuclear Magnetic Resonance experiments. On the study of six two-domain protein chimeras as well as their composing domains and their x-ray structures selected from PDB, we conclude that the major obstacle for justified prediction is inappropriate sampling of the conformational space by the explored methods. On the other hands, we can still address particular steps of the methodology and improve the process of chimera proteins prediction.
ER  -

VYMETAL, Jiri; Katerina MERTOVA; Kristyna BOUSOVA; Josef SULC; Konstantinos TRIPSIANES a Jiri VONDRASEK. Fusion of two unrelated protein domains in a chimera protein and its 3D prediction: Justification of the x-ray reference structures as a prediction benchmark. \textit{Proteins: Structure, Function, and Bioinformatics}. 2022, roč.~90, č.~12, s.~2067-2079. ISSN~0887-3585. Dostupné z: https://doi.org/10.1002/prot.26398.

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