Comparison of the molecular properties of retinitis pigmentosa
P23H and N15S amino acid replacements in rhodopsin

J 2019

Comparison of the molecular properties of retinitis pigmentosa P23H and N15S amino acid replacements in rhodopsin

MITCHELL, James, Fernanda BALEM, Kalyan TIRUPULA, David MAN, Harpreet Kaur DHIMAN et. al.

Basic information

Original name

Comparison of the molecular properties of retinitis pigmentosa P23H and N15S amino acid replacements in rhodopsin

Authors

MITCHELL, James, Fernanda BALEM, Kalyan TIRUPULA, David MAN, Harpreet Kaur DHIMAN, Naveena YANAMALA, Julian OLLESCH, Joan PLANAS IGLESIAS (724 Spain, belonging to the institution), Barbara J. JENNINGS, Klaus GERWERT, Alessandro IANNACCONE and Judith KLEIN-SEETHARAMAN (guarantor)

Edition

Plos one, San Francisco, Public Library of Science, 2019, 1932-6203

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10606 Microbiology

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 2.740

RIV identification code

RIV/00216224:14310/19:00113531

Organization unit

Faculty of Science

DOI

http://dx.doi.org/10.1371/journal.pone.0214639

UT WoS

000468176600003

Keywords in English

POINT MUTATION; VITAMIN-A; MUTANTS; GENE; EXPRESSION; SUPPLEMENTATION; GLYCOSYLATION; IMPROVEMENT; STABILITY; BINDING

Abstract

V originále

Mutations in the RHO gene encoding for the visual pigment protein, rhodopsin, are among the most common cause of autosomal dominant retinitis pigmentosa (ADRP). Previous studies of ADRP mutations in different domains of rhodopsin have indicated that changes that lead to more instability in rhodopsin structure are responsible for more severe disease in patients. Here, we further test this hypothesis by comparing side-by-side and therefore quantitatively two RHO mutations, N15S and P23H, both located in the N-terminal intradiscal domain. The in vitro biochemical properties of these two rhodopsin proteins, expressed in stably transfected tetracycline-inducible HEK293S cells, their UV-visible absorption, their Fourier transform infrared, circular dichroism and Metarhodopsin II fluorescence spectroscopy properties were characterized. As compared to the severely impaired P23H molecular function, N15S is only slightly defective in structure and stability. We propose that the molecular basis for these structural differences lies in the greater distance of the N15 residue as compared to P23 with respect to the predicted rhodopsin folding core. As described previously for WT rhodopsin, addition of the cytoplasmic allosteric modulator chlorin e6 stabilizes especially the P23H protein, suggesting that chlorin e6 may be generally beneficial in the rescue of those ADRP rhodopsin proteins whose stability is affected by amino acid replacement.

Citovat

MITCHELL, James, Fernanda BALEM, Kalyan TIRUPULA, David MAN, Harpreet Kaur DHIMAN, Naveena YANAMALA, Julian OLLESCH, Joan PLANAS IGLESIAS, Barbara J. JENNINGS, Klaus GERWERT, Alessandro IANNACCONE and Judith KLEIN-SEETHARAMAN. Comparison of the molecular properties of retinitis pigmentosa P23H and N15S amino acid replacements in rhodopsin. Plos one. San Francisco: Public Library of Science, 2019, vol. 14, No 5, p. 1-14. ISSN 1932-6203. Available from: https://dx.doi.org/10.1371/journal.pone.0214639.

@article{1642440,
   author = {Mitchell, James and Balem, Fernanda and Tirupula, Kalyan and Man, David and Dhiman, Harpreet Kaur and Yanamala, Naveena and Ollesch, Julian and Planas Iglesias, Joan and Jennings, Barbara J. and Gerwert, Klaus and Iannaccone, Alessandro and KleinandSeetharaman, Judith},
   article_location = {San Francisco},
   article_number = {5},
   doi = {http://dx.doi.org/10.1371/journal.pone.0214639},
   keywords = {POINT MUTATION; VITAMIN-A; MUTANTS; GENE; EXPRESSION; SUPPLEMENTATION; GLYCOSYLATION; IMPROVEMENT; STABILITY; BINDING},
   language = {eng},
   issn = {1932-6203},
   journal = {Plos one},
   title = {Comparison of the molecular properties of retinitis pigmentosa P23H and N15S amino acid replacements in rhodopsin},
   url = {https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0214639},
   volume = {14},
   year = {2019}
}

TY  - JOUR
ID  - 1642440
AU  - Mitchell, James - Balem, Fernanda - Tirupula, Kalyan - Man, David - Dhiman, Harpreet Kaur - Yanamala, Naveena - Ollesch, Julian - Planas Iglesias, Joan - Jennings, Barbara J. - Gerwert, Klaus - Iannaccone, Alessandro - Klein-Seetharaman, Judith
PY  - 2019
TI  - Comparison of the molecular properties of retinitis pigmentosa P23H and N15S amino acid replacements in rhodopsin
JF  - Plos one
VL  - 14
IS  - 5
SP  - 1-14
EP  - 1-14
PB  - Public Library of Science
SN  - 19326203
KW  - POINT MUTATION
KW  - VITAMIN-A
KW  - MUTANTS
KW  - GENE
KW  - EXPRESSION
KW  - SUPPLEMENTATION
KW  - GLYCOSYLATION
KW  - IMPROVEMENT
KW  - STABILITY
KW  - BINDING
UR  - https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0214639
L2  - https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0214639
N2  - Mutations in the RHO gene encoding for the visual pigment protein, rhodopsin, are among the most common cause of autosomal dominant retinitis pigmentosa (ADRP). Previous studies of ADRP mutations in different domains of rhodopsin have indicated that changes that lead to more instability in rhodopsin structure are responsible for more severe disease in patients. Here, we further test this hypothesis by comparing side-by-side and therefore quantitatively two RHO mutations, N15S and P23H, both located in the N-terminal intradiscal domain. The in vitro biochemical properties of these two rhodopsin proteins, expressed in stably transfected tetracycline-inducible HEK293S cells, their UV-visible absorption, their Fourier transform infrared, circular dichroism and Metarhodopsin II fluorescence spectroscopy properties were characterized. As compared to the severely impaired P23H molecular function, N15S is only slightly defective in structure and stability. We propose that the molecular basis for these structural differences lies in the greater distance of the N15 residue as compared to P23 with respect to the predicted rhodopsin folding core. As described previously for WT rhodopsin, addition of the cytoplasmic allosteric modulator chlorin e6 stabilizes especially the P23H protein, suggesting that chlorin e6 may be generally beneficial in the rescue of those ADRP rhodopsin proteins whose stability is affected by amino acid replacement.
ER  -

MITCHELL, James, Fernanda BALEM, Kalyan TIRUPULA, David MAN, Harpreet Kaur DHIMAN, Naveena YANAMALA, Julian OLLESCH, Joan PLANAS IGLESIAS, Barbara J. JENNINGS, Klaus GERWERT, Alessandro IANNACCONE and Judith KLEIN-SEETHARAMAN. Comparison of the molecular properties of retinitis pigmentosa P23H and N15S amino acid replacements in rhodopsin. \textit{Plos one}. San Francisco: Public Library of Science, 2019, vol.~14, No~5, p.~1-14. ISSN~1932-6203. Available from: https://dx.doi.org/10.1371/journal.pone.0214639.

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