Functional analysis of the p.(Leu15Pro) and p.(Gly20Arg) sequence changes in the signal sequence of LDL receptor

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00209775%3A_____%2F16%3AN0000018" target="_blank" >RIV/00209775:_____/16:N0000018 - isvavai.cz</a>

Alternative codes found

RIV/00216224:14740/16:00087619 RIV/65269705:_____/16:00066094

Result on the web

<a href="http://dx.doi.org/10.1016/j.atherosclerosis.2016.04.022" target="_blank" >http://dx.doi.org/10.1016/j.atherosclerosis.2016.04.022</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.atherosclerosis.2016.04.022" target="_blank" >10.1016/j.atherosclerosis.2016.04.022</a>

Result language

angličtina

Original language name

Functional analysis of the p.(Leu15Pro) and p.(Gly20Arg) sequence changes in the signal sequence of LDL receptor

Original language description

The low density lipoprotein receptor (LDLR) is a transmembrane protein that plays a key role in cholesterol metabolism. It contains 860 amino acids including a 21 amino acid long signal sequence, which directs the protein into the endoplasmic reticulum. Mutations in the LDLR gene lead to cholesterol accumulation in the plasma and results in familial hypercholesterolemia (FH). Knowledge of the impact of a mutation on the LDLR protein structure and function is very important for the diagnosis and management of FH. Unfortunately, for a large proportion of mutations this information is still missing. In this study, we focused on the LDLR signal sequence and carried out functional and in silico analyses of two sequence changes, p.(Gly20Arg) and p.(Leu15Pro), localized in this part of the LDLR. Our results revealed that the p.(Gly20Arg) change, previously described as disease causing, has no detrimental effect on protein expression or LDL particle binding. In silico analysis supports this observation, showing that both the wt and p.(Gly20Arg) signal sequences adopt an expected α-helix structure. In contrast, the mutation p.(Leu15Pro) is not associated with functional protein expression and exhibits a structure with disrupted a α-helical arrangement in the signal sequence, which most likely affects protein folding in the endoplasmic reticulum.

Czech name

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Czech description

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Type

J_x - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

CEP classification

FB - Endocrinology, diabetology, metabolism, nutrition

OECD FORD branch

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Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

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

Publication year

2016

Confidentiality

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

Name of the periodical

Atherosclerosis

ISSN

0021-9150

e-ISSN

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Volume of the periodical

250

Issue of the periodical within the volume

July

Country of publishing house

NL - THE KINGDOM OF THE NETHERLANDS

Number of pages

6

Pages from-to

9-14

UT code for WoS article

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EID of the result in the Scopus database

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