New penta-saccharide-bearing tripod amphiphiles for membrane protein structure studies

Muhammad Ehsan; Lubna Ghani; Yang Du; Parameswaran Hariharan; Jonas S. Mortensen; Orquidea Ribeiro; Hongli Hu; Georgios Skiniotis; Claus J. Loland; Lan Guan; Brian K. Kobilka; Bernadette Byrne; Pil Seok Chae

doi:10.1039/c7an01168g

New penta-saccharide-bearing tripod amphiphiles for membrane protein structure studies

Muhammad Ehsan, Lubna Ghani, Yang Du, Parameswaran Hariharan, Jonas S. Mortensen, Orquidea Ribeiro, Hongli Hu, Georgios Skiniotis, Claus J. Loland, Lan Guan, Brian K. Kobilka, Bernadette Byrne, Pil Seok Chae^*

^*Corresponding author for this work

Neuropharm and Genetics

5 Citations (Scopus)

Abstract

Integral membrane proteins either alone or as complexes carry out a range of key cellular functions. Detergents are indispensable tools in the isolation of membrane proteins from biological membranes for downstream studies. Although a large number of techniques and tools, including a wide variety of detergents, are available, purification and structural characterization of many membrane proteins remain challenging. In the current study, a new class of tripod amphiphiles bearing two different penta-saccharide head groups, designated TPSs, were developed and evaluated for their ability to extract and stabilize a range of diverse membrane proteins. Variations in the structures of the detergent head and tail groups allowed us to prepare three sets of the novel agents with distinctive structures. Some TPSs (TPS-A8 and TPS-E7) were efficient at extracting two proteins in a functional state while others (TPS-E8 and TPS-E10L) conferred marked stability to all membrane proteins (and membrane protein complexes) tested here compared to a conventional detergent. Use of TPS-E10L led to clear visualization of a receptor-G_s complex using electron microscopy, indicating profound potential in membrane protein research.

Original language	English
Journal	Analyst
Volume	142
Issue number	20
Pages (from-to)	3889-3898
Number of pages	10
ISSN	0003-2654
DOIs	https://doi.org/10.1039/c7an01168g
Publication status	Published - Oct 2017

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title = "New penta-saccharide-bearing tripod amphiphiles for membrane protein structure studies",

abstract = "Integral membrane proteins either alone or as complexes carry out a range of key cellular functions. Detergents are indispensable tools in the isolation of membrane proteins from biological membranes for downstream studies. Although a large number of techniques and tools, including a wide variety of detergents, are available, purification and structural characterization of many membrane proteins remain challenging. In the current study, a new class of tripod amphiphiles bearing two different penta-saccharide head groups, designated TPSs, were developed and evaluated for their ability to extract and stabilize a range of diverse membrane proteins. Variations in the structures of the detergent head and tail groups allowed us to prepare three sets of the novel agents with distinctive structures. Some TPSs (TPS-A8 and TPS-E7) were efficient at extracting two proteins in a functional state while others (TPS-E8 and TPS-E10L) conferred marked stability to all membrane proteins (and membrane protein complexes) tested here compared to a conventional detergent. Use of TPS-E10L led to clear visualization of a receptor-Gs complex using electron microscopy, indicating profound potential in membrane protein research.",

author = "Muhammad Ehsan and Lubna Ghani and Yang Du and Parameswaran Hariharan and Mortensen, {Jonas S.} and Orquidea Ribeiro and Hongli Hu and Georgios Skiniotis and Loland, {Claus J.} and Lan Guan and Kobilka, {Brian K.} and Bernadette Byrne and Chae, {Pil Seok}",

year = "2017",

month = oct,

doi = "10.1039/c7an01168g",

language = "English",

volume = "142",

pages = "3889--3898",

journal = "The Analyst",

issn = "0003-2654",

publisher = "Royal Society of Chemistry",

number = "20",

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TY - JOUR

T1 - New penta-saccharide-bearing tripod amphiphiles for membrane protein structure studies

AU - Ehsan, Muhammad

AU - Ghani, Lubna

AU - Du, Yang

AU - Hariharan, Parameswaran

AU - Mortensen, Jonas S.

AU - Ribeiro, Orquidea

AU - Hu, Hongli

AU - Skiniotis, Georgios

AU - Loland, Claus J.

AU - Guan, Lan

AU - Kobilka, Brian K.

AU - Byrne, Bernadette

AU - Chae, Pil Seok

PY - 2017/10

Y1 - 2017/10

N2 - Integral membrane proteins either alone or as complexes carry out a range of key cellular functions. Detergents are indispensable tools in the isolation of membrane proteins from biological membranes for downstream studies. Although a large number of techniques and tools, including a wide variety of detergents, are available, purification and structural characterization of many membrane proteins remain challenging. In the current study, a new class of tripod amphiphiles bearing two different penta-saccharide head groups, designated TPSs, were developed and evaluated for their ability to extract and stabilize a range of diverse membrane proteins. Variations in the structures of the detergent head and tail groups allowed us to prepare three sets of the novel agents with distinctive structures. Some TPSs (TPS-A8 and TPS-E7) were efficient at extracting two proteins in a functional state while others (TPS-E8 and TPS-E10L) conferred marked stability to all membrane proteins (and membrane protein complexes) tested here compared to a conventional detergent. Use of TPS-E10L led to clear visualization of a receptor-Gs complex using electron microscopy, indicating profound potential in membrane protein research.

AB - Integral membrane proteins either alone or as complexes carry out a range of key cellular functions. Detergents are indispensable tools in the isolation of membrane proteins from biological membranes for downstream studies. Although a large number of techniques and tools, including a wide variety of detergents, are available, purification and structural characterization of many membrane proteins remain challenging. In the current study, a new class of tripod amphiphiles bearing two different penta-saccharide head groups, designated TPSs, were developed and evaluated for their ability to extract and stabilize a range of diverse membrane proteins. Variations in the structures of the detergent head and tail groups allowed us to prepare three sets of the novel agents with distinctive structures. Some TPSs (TPS-A8 and TPS-E7) were efficient at extracting two proteins in a functional state while others (TPS-E8 and TPS-E10L) conferred marked stability to all membrane proteins (and membrane protein complexes) tested here compared to a conventional detergent. Use of TPS-E10L led to clear visualization of a receptor-Gs complex using electron microscopy, indicating profound potential in membrane protein research.

U2 - 10.1039/c7an01168g

DO - 10.1039/c7an01168g

M3 - Journal article

C2 - 28913526

AN - SCOPUS:85031011601

SN - 0003-2654

VL - 142

SP - 3889

EP - 3898

JO - The Analyst

JF - The Analyst

IS - 20

ER -

New penta-saccharide-bearing tripod amphiphiles for membrane protein structure studies

Abstract

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