De novo design of a non-local beta-sheet protein with high stability and accuracy

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14740%2F18%3A00104596" target="_blank" >RIV/00216224:14740/18:00104596 - isvavai.cz</a>

Výsledek na webu

<a href="http://dx.doi.org/10.1038/s41594-018-0141-6" target="_blank" >http://dx.doi.org/10.1038/s41594-018-0141-6</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/s41594-018-0141-6" target="_blank" >10.1038/s41594-018-0141-6</a>

Jazyk výsledku

angličtina

Název v původním jazyce

De novo design of a non-local beta-sheet protein with high stability and accuracy

Popis výsledku v původním jazyce

beta-sheet proteins carry out critical functions in biology, and hence are attractive scaffolds for computational protein design. Despite this potential, de novo design of all-beta-sheet proteins from first principles lags far behind the design of all-alpha or mixed-alpha beta domains owing to their non-local nature and the tendency of exposed beta-strand edges to aggregate. Through study of loops connecting unpaired beta-strands (beta-arches), we have identified a series of structural relationships between loop geometry, side chain directionality and beta-strand length that arise from hydrogen bonding and packing constraints on regular beta-sheet structures. We use these rules to de novo design jellyroll structures with double-stranded beta-helices formed by eight antiparallel beta-strands. The nuclear magnetic resonance structure of a hyperthermostable design closely matched the computational model, demonstrating accurate control over the beta-sheet structure and loop geometry. Our results open the door to the design of a broad range of non-local beta-sheet protein structures.

Název v anglickém jazyce

De novo design of a non-local beta-sheet protein with high stability and accuracy

Popis výsledku anglicky

beta-sheet proteins carry out critical functions in biology, and hence are attractive scaffolds for computational protein design. Despite this potential, de novo design of all-beta-sheet proteins from first principles lags far behind the design of all-alpha or mixed-alpha beta domains owing to their non-local nature and the tendency of exposed beta-strand edges to aggregate. Through study of loops connecting unpaired beta-strands (beta-arches), we have identified a series of structural relationships between loop geometry, side chain directionality and beta-strand length that arise from hydrogen bonding and packing constraints on regular beta-sheet structures. We use these rules to de novo design jellyroll structures with double-stranded beta-helices formed by eight antiparallel beta-strands. The nuclear magnetic resonance structure of a hyperthermostable design closely matched the computational model, demonstrating accurate control over the beta-sheet structure and loop geometry. Our results open the door to the design of a broad range of non-local beta-sheet protein structures.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

<a href="/cs/project/LQ1601" target="_blank" >LQ1601: CEITEC 2020</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2018

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

NATURE STRUCTURAL &amp; MOLECULAR BIOLOGY

ISSN

1545-9993

e-ISSN

—

Svazek periodika

25

Číslo periodika v rámci svazku

11

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

10

Strana od-do

1028

Kód UT WoS článku

000449271800009

EID výsledku v databázi Scopus

2-s2.0-85055985092