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Comparison of fragments comprising the first two helices of the human Y4 and the yeast Ste2p G-protein-coupled receptors


Shao, X; Zou, C; Naider, F; Zerbe, O (2012). Comparison of fragments comprising the first two helices of the human Y4 and the yeast Ste2p G-protein-coupled receptors. Biophysical Journal, 103(4):817-826.

Abstract

Solution NMR techniques are used to determine the structure and the topology of micelle integration of a large fragment of the Y4 receptor, a human G-protein-coupled receptor, that contains the entire N-terminal domain plus the first two transmembrane (TM) segments. The structure calculations reveal that the putative TM helices are indeed helical to a large extent, but that interruptions of secondary structure occur close to internal polar or charged residues. This view is supported by 15N relaxation data, amide-water exchange rates, and attenuations from micelle-integrating spin labels. No contacts between different helices are observed. This is in contrast to a similar TM1-TM2 fragment from the yeast Ste2p receptor for which locations of the secondary and the tertiary structure agreed well with the predictions from a homology model. The difference in structure is discussed in terms of principal biophysical properties of residues within central regions of the putative TM helices. Overall, using the biophysical scale of Wimley and White the TM regions of Ste2p display much more favorable free energies for membrane integration. Accordingly, the full secondary structure and the tertiary structure in TM1-TM2 of the Y4 receptor is likely to be formed only when tertiary contacts with other TM segments are created during folding of the receptor.

Solution NMR techniques are used to determine the structure and the topology of micelle integration of a large fragment of the Y4 receptor, a human G-protein-coupled receptor, that contains the entire N-terminal domain plus the first two transmembrane (TM) segments. The structure calculations reveal that the putative TM helices are indeed helical to a large extent, but that interruptions of secondary structure occur close to internal polar or charged residues. This view is supported by 15N relaxation data, amide-water exchange rates, and attenuations from micelle-integrating spin labels. No contacts between different helices are observed. This is in contrast to a similar TM1-TM2 fragment from the yeast Ste2p receptor for which locations of the secondary and the tertiary structure agreed well with the predictions from a homology model. The difference in structure is discussed in terms of principal biophysical properties of residues within central regions of the putative TM helices. Overall, using the biophysical scale of Wimley and White the TM regions of Ste2p display much more favorable free energies for membrane integration. Accordingly, the full secondary structure and the tertiary structure in TM1-TM2 of the Y4 receptor is likely to be formed only when tertiary contacts with other TM segments are created during folding of the receptor.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:07 Faculty of Science > Department of Chemistry
Dewey Decimal Classification:540 Chemistry
Uncontrolled Keywords:GPCR Ste2p NMR GPCR fragment membrane protein
Language:English
Date:2012
Deposited On:12 Sep 2012 08:47
Last Modified:05 Apr 2016 15:56
Publisher:Elsevier
ISSN:0006-3495
Funders:Swiss National Science Foundation, OPO Foundation
Publisher DOI:https://doi.org/10.1016/j.bpj.2012.07.012
PubMed ID:22947943
Permanent URL: https://doi.org/10.5167/uzh-64490

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