PDBsum entry: 3d4s

Membrane protein

PDB-id

3d4s


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Description

Header details

Protein chain

Ligands

TIM

CLR ×2

OLC ×3

Waters ×20

* Residue conservation analysis

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PDB id:

3d4s

Name:

Membrane protein

Title:

Cholesterol bound form of human beta2 adrenergic receptor.

Structure:

Beta-2 adrenergic receptor/t4-lysozyme chimera. Chain: a. Synonym: beta-2 adrenoceptor, beta-2 adrenoreceptor / lysis protein, muramidase, endolysin. Engineered: yes. Mutation: yes

Source:

Homo sapiens, bacteriophage t4. Organism_taxid: 9606. Gene: adrb2, adrb2r, b2ar / e. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108.

UniProt:

P00720 (LYS_BPT4)

Seq:

Struc:


Seq:				164 a.a.

Struc:				439 a.a.*

P07550 (ADRB2_HUMAN)

Seq:

Struc:

Seq:

413 a.a.

Struc:

439 a.a.*

Key:		PfamA domain
		Secondary structure			CATH domain

* PDB and UniProt seqs differ at 155 residue positions (black crosses)

Resolution:

2.80Å

R-factor:

0.230

R-free:

0.273

Authors:

M.A.Hanson,V.Cherezov,C.B.Roth,M.T.Griffith,V-P.Jaakola, E.Y.T.Chien,J.Velasquez,P.Kuhn,R.C.Stevens,Accelerated Technologies Center For Gene To 3d Structure (Atcg3d)

Key ref:

M.A.Hanson et al. (2008). A specific cholesterol binding site is established by the 2.8 A structure of the human beta2-adrenergic receptor.. Structure, 16, 897-905. [PubMed id: 18547522] [DOI: 10.1016/j.str.2008.05.001]

Date:

14-May-08

Release date:

17-Jun-08

Related entries:

2rh1
high resolution crystal structure of human b2-adrenergic g
protein-coupled receptor
atcg3d_18 related db: targetdb

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Key reference

DOI no: 10.1016/j.str.2008.05.001 Structure 16:897-905 (2008)

PubMed id: 18547522

A specific cholesterol binding site is established by the 2.8 A structure of the human beta2-adrenergic receptor.

M.A.Hanson, V.Cherezov, M.T.Griffith, C.B.Roth, V.P.Jaakola, E.Y.Chien, J.Velasquez, P.Kuhn, R.C.Stevens.

ABSTRACT

The role of cholesterol in eukaryotic membrane protein function has been attributed primarily to an influence on membrane fluidity and curvature. We present the 2.8 A resolution crystal structure of a thermally stabilized human beta(2)-adrenergic receptor bound to cholesterol and the partial inverse agonist timolol. The receptors pack as monomers in an antiparallel association with two distinct cholesterol molecules bound per receptor, but not in the packing interface, thereby indicating a structurally relevant cholesterol-binding site between helices I, II, III, and IV. Thermal stability analysis using isothermal denaturation confirms that a cholesterol analog significantly enhances the stability of the receptor. A consensus motif is defined that predicts cholesterol binding for 44% of human class A receptors, suggesting that specific sterol binding is important to the structure and stability of other G protein-coupled receptors, and that this site may provide a target for therapeutic discovery.

Literature references that cite this PDB file's key reference

PubMed id Reference

19451648 B.Ilien, N.Glasser, J.P.Clamme, P.Didier, E.Piemont, R.Chinnappan, S.B.Daval, J.L.Galzi, and Y.Mely (2009).
Pirenzepine Promotes the Dimerization of Muscarinic M1 Receptors through a Three-step Binding Process.

J Biol Chem, 284, 19533-19543.

19458711 D.M.Rosenbaum, S.G.Rasmussen, and B.K.Kobilka (2009).
The structure and function of G-protein-coupled receptors.

Nature, 459, 356-363.

19339946 D.T.Lodowski, and K.Palczewski (2009).
Chemokine receptors and other G protein-coupled receptors.

Curr Opin HIV AIDS, 4, 88-95.

19192200 D.T.Lodowski, T.E.Angel, and K.Palczewski (2009).
Comparative Analysis of GPCR Crystal Structures.

Photochem Photobiol, 85, 425-430.

19339947 G.Alkhatib (2009).
The biology of CCR5 and CXCR4.

Curr Opin HIV AIDS, 4, 96.

19173312 G.Khelashvili, A.Grossfield, S.E.Feller, M.C.Pitman, and H.Weinstein (2009).
Structural and dynamic effects of cholesterol at preferred sites of interaction with rhodopsin identified from microsecond length molecular dynamics simulations.

Proteins, 76, 403-417.

19706508 I.A.Balabin, W.Yang, and D.N.Beratan (2009).
Coarse-grained modeling of allosteric regulation in protein receptors.

Proc Natl Acad Sci U S A, 106, 14253-14258.

19378355 J.Huszár, Z.Timár, F.Bogár, B.Penke, R.Kiss, K.K.Szalai, E.Schmidt, A.Papp, and G.Keseru (2009).
Aspartic acid scaffold in bradykinin B1 antagonists.

J Pept Sci, 15, 423-434.

19263094 M.A.Soriano-Ursúa, J.G.Trujillo-Ferrara, and J.Correa-Basurto (2009).
Homology modeling and flex-ligand docking studies on the guinea pig beta(2) adrenoceptor: structural and experimental similarities/ differences with the human beta(2).

J Mol Model, 15, 1203-1211.

19258456 R.O.Dror, D.H.Arlow, D.W.Borhani, M.�.�.Jensen, S.Piana, and D.E.Shaw (2009).
Identification of two distinct inactive conformations of the beta2-adrenergic receptor reconciles structural and biochemical observations.

Proc Natl Acad Sci U S A, 106, 4689-4694.

19291412 S.Ananthan, W.Zhang, and J.V.Hobrath (2009).
Recent advances in structure-based virtual screening of G-protein coupled receptors.

AAPS J, 11, 178-185.

19262747 S.N.Fatakia, S.Costanzi, and C.C.Chow (2009).
Computing highly correlated positions using mutual information and graph theory for G protein-coupled receptors.

PLoS ONE, 4, e4681.

19535414 V.Cherezov, M.A.Hanson, M.T.Griffith, M.C.Hilgart, R.Sanishvili, V.Nagarajan, S.Stepanov, R.F.Fischetti, P.Kuhn, and R.C.Stevens (2009).
Rastering strategy for screening and centring of microcrystal samples of human membrane proteins with a sub-10 microm size X-ray synchrotron beam.

J R Soc Interface, 6, S587-S597.

19353579 V.Katritch, K.A.Reynolds, V.Cherezov, M.A.Hanson, C.B.Roth, M.Yeager, and R.Abagyan (2009).
Analysis of full and partial agonists binding to beta2-adrenergic receptor suggests a role of transmembrane helix V in agonist-specific conformational changes.

J Mol Recognit, 22, 307-318.

18832607 V.P.Jaakola, M.T.Griffith, M.A.Hanson, V.Cherezov, E.Y.Chien, J.R.Lane, A.P.Ijzerman, and R.C.Stevens (2008).
The 2.6 angstrom crystal structure of a human A2A adenosine receptor bound to an antagonist.

Science, 322, 1211-1217.

PDB code: 3eml

The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.