Functional studies of isolated GPCR-G protein complexes in the membrane bilayer of lipoprotein particles

TY - CHAP

T1 - Functional studies of isolated GPCR-G protein complexes in the membrane bilayer of lipoprotein particles

AU - Kuszak, A. J.

AU - Yao, Xiao Jie

AU - Rasmussen, Søren Gøgsig Faarup

AU - Kobilka, Brian

AU - Sunahara, Roger K

PY - 2010/1/1

Y1 - 2010/1/1

N2 - INTRODUCTION Over the past few years we have witnessed a dramatic expansion of our knowledge of G protein-coupled receptor GPCR structure and function. This increased understanding has been driven by the development of novel techniques that allow further characterization of GPCRs at an atomic level. A veritable opening of the floodgates has occurred with the reports of multiple crystal structures for GPCRs, including the β 2 adrenoceptor (AR) bound to partial inverse agonists,– the β 1AR bound to an antagonist, the A2A adenosine receptor, and new structures of opsin.– These structures have provided insight into the various GPCR conformational states stabilized by ligands, and also suggest important mechanisms of G protein coupling and activation (see Chapter 1). Although highly informative, one must remember that crystal structures provide static images of proteins and may be influenced by packing of the crystal lattice. However, GPCRs are dynamic molecules, undergoing both dramatic and subtle conformational changes during their activation process. Accordingly, crystallographic information must be supplemented with an understanding of the functional interaction between GPCRs and G protein heterotrimers. Recent technological advances in membrane protein biochemistry have led to significant enhancements in our understanding of GPCR function. These advancements have been driven by the work of multiple laboratories probing the structure and function of isolated GPCRs in reconstituted lipoprotein particles, which are derived from high density lipoprotein (HDL) particles. This novel methodology utilizes purified GPCRs isolated in a phospholipid bilayer, a mimic of their native plasma membrane environment.

AB - INTRODUCTION Over the past few years we have witnessed a dramatic expansion of our knowledge of G protein-coupled receptor GPCR structure and function. This increased understanding has been driven by the development of novel techniques that allow further characterization of GPCRs at an atomic level. A veritable opening of the floodgates has occurred with the reports of multiple crystal structures for GPCRs, including the β 2 adrenoceptor (AR) bound to partial inverse agonists,– the β 1AR bound to an antagonist, the A2A adenosine receptor, and new structures of opsin.– These structures have provided insight into the various GPCR conformational states stabilized by ligands, and also suggest important mechanisms of G protein coupling and activation (see Chapter 1). Although highly informative, one must remember that crystal structures provide static images of proteins and may be influenced by packing of the crystal lattice. However, GPCRs are dynamic molecules, undergoing both dramatic and subtle conformational changes during their activation process. Accordingly, crystallographic information must be supplemented with an understanding of the functional interaction between GPCRs and G protein heterotrimers. Recent technological advances in membrane protein biochemistry have led to significant enhancements in our understanding of GPCR function. These advancements have been driven by the work of multiple laboratories probing the structure and function of isolated GPCRs in reconstituted lipoprotein particles, which are derived from high density lipoprotein (HDL) particles. This novel methodology utilizes purified GPCRs isolated in a phospholipid bilayer, a mimic of their native plasma membrane environment.

M3 - Book chapter

SN - 978-0-521-11208-6

SP - 32

EP - 52

BT - G Protein-Coupled Receptors

PB - Cambridge University Press

ER -