7SQ2

Reprocessed and refined structure of Phospholipase C-beta and Gq signaling complex

PDB DOI: https://doi.org/10.2210/pdb7SQ2/pdb
Entry: 7SQ2 supersedes: 3OHM

Classification: SIGNALING PROTEIN
Organism(s): Mus musculus, Homo sapiens
Expression System: Spodoptera frugiperda
Mutation(s): No

Deposited: 2021-11-04 Released: 2021-11-17
Deposition Author(s): Endo-Streeter, S.T., Sondek, J., Harden, T.K.
Funding Organization(s): National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS), National Institutes of Health/National Eye Institute (NIH/NEI)

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 2.60 Å
R-Value Free: 0.263
R-Value Work: 0.199
R-Value Observed: 0.202

wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

This is version 1.1 of the entry. See complete history.

Re-refinement Note

This entry reflects an alternative modeling of the original data in: 3OHM

Literature

Kinetic Scaffolding Mediated by a Phospholipase C-{beta} and Gq Signaling Complex

Endo-Streeter, S.T., Sondek, J., Harden, T.K.

(2010) Science 330: 974-980

PubMed: 20966218 Search on PubMedSearch on PubMed Central
DOI: https://doi.org/10.1126/science.1193438
Primary Citation of Related Structures:
7SQ2

PubMed Abstract:
Transmembrane signals initiated by a broad range of extracellular stimuli converge on nodes that regulate phospholipase C (PLC)-dependent inositol lipid hydrolysis for signal propagation. We describe how heterotrimeric guanine nucleotide-binding proteins (G proteins) activate PLC-βs and in turn are deactivated by these downstream effectors. The 2.7-angstrom structure of PLC-β3 bound to activated Gα(q) reveals a conserved module found within PLC-βs and other effectors optimized for rapid engagement of activated G proteins. The active site of PLC-β3 in the complex is occluded by an intramolecular plug that is likely removed upon G protein-dependent anchoring and orientation of the lipase at membrane surfaces. A second domain of PLC-β3 subsequently accelerates guanosine triphosphate hydrolysis by Gα(q), causing the complex to dissociate and terminate signal propagation. Mutations within this domain dramatically delay signal termination in vitro and in vivo. Consequently, this work suggests a dynamic catch-and-release mechanism used to sharpen spatiotemporal signals mediated by diverse sensory inputs.

Organizational Affiliation

Department of Pharmacology, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.

Macromolecule Content

Total Structure Weight: 139.17 kDa
Atom Count: 8,957
Modelled Residue Count: 1,072
Deposited Residue Count: 1,212
Unique protein chains: 2

Macromolecules

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
Guanine nucleotide-binding protein G(q) subunit alpha	A	327	Mus musculus	Mutation(s): 0 Gene Names: Gnaq
UniProt
Find proteins for P21279 (Mus musculus) Explore P21279 Go to UniProtKB: P21279
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P21279
Sequence Annotations Expand
Reference Sequence

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 2
Molecule	Chains	Sequence Length	Organism	Details	Image
1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3	B	885	Homo sapiens	Mutation(s): 0 Gene Names: PLCB3 EC: 3.1.4.11
UniProt & NIH Common Fund Data Resources
Find proteins for Q01970 (Homo sapiens) Explore Q01970 Go to UniProtKB: Q01970
PHAROS: Q01970 GTEx: ENSG00000149782
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	Q01970
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 5 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
GDP (Subject of Investigation/LOI) Query on GDP Download Ideal Coordinates CCD File SDF format, chain E [auth A] MOL2 format, chain E [auth A]	E [auth A]	GUANOSINE-5'-DIPHOSPHATE C₁₀ H₁₅ N₅ O₁₁ P₂ QGWNDRXFNXRZMB-UUOKFMHZSA-N		Interactions Focus chain E [auth A] Interactions & Density Focus chain E [auth A]
ALF (Subject of Investigation/LOI) Query on ALF Download Ideal Coordinates CCD File SDF format, chain C [auth A] MOL2 format, chain C [auth A]	C [auth A]	TETRAFLUOROALUMINATE ION Al F₄ UYOMQIYKOOHAMK-UHFFFAOYSA-J		Interactions Focus chain C [auth A] Interactions & Density Focus chain C [auth A]
ACT Query on ACT Download Ideal Coordinates CCD File SDF format, chain F [auth A] SDF format, chain G [auth B] SDF format, chain H [auth B] SDF format, chain I [auth B] SDF format, chain J [auth B] SDF format, chain K [auth B] SDF format, chain L [auth B] MOL2 format, chain F [auth A] MOL2 format, chain G [auth B] MOL2 format, chain H [auth B] MOL2 format, chain I [auth B] MOL2 format, chain J [auth B] MOL2 format, chain K [auth B] MOL2 format, chain L [auth B]	F [auth A] G [auth B] H [auth B] I [auth B] J [auth B] F [auth A], G [auth B], H [auth B], I [auth B], J [auth B], K [auth B], L [auth B]	ACETATE ION C₂ H₃ O₂ QTBSBXVTEAMEQO-UHFFFAOYSA-M		Interactions Focus chain F [auth A] Focus chain G [auth B] Focus chain H [auth B] Focus chain I [auth B] Focus chain J [auth B] Focus chain K [auth B] Focus chain L [auth B] Interactions & Density Focus chain F [auth A] Focus chain G [auth B] Focus chain H [auth B] Focus chain I [auth B] Focus chain J [auth B] Focus chain K [auth B] Focus chain L [auth B]
CA (Subject of Investigation/LOI) Query on CA Download Ideal Coordinates CCD File SDF format, chain M [auth B] MOL2 format, chain M [auth B]	M [auth B]	CALCIUM ION Ca BHPQYMZQTOCNFJ-UHFFFAOYSA-N		Interactions Focus chain M [auth B] Interactions & Density Focus chain M [auth B]
MG (Subject of Investigation/LOI) Query on MG Download Ideal Coordinates CCD File SDF format, chain D [auth A] SDF format, chain N [auth B] MOL2 format, chain D [auth A] MOL2 format, chain N [auth B]	D [auth A], N [auth B]	MAGNESIUM ION Mg JLVVSXFLKOJNIY-UHFFFAOYSA-N		Interactions Focus chain D [auth A] Focus chain N [auth B] Interactions & Density Focus chain D [auth A] Focus chain N [auth B]

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 2.60 Å
R-Value Free: 0.263
R-Value Work: 0.199
R-Value Observed: 0.202
Space Group: C 1 2 1

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 202.837	α = 90
b = 90.817	β = 101.19
c = 93.135	γ = 90

Software Package:

Software Name	Purpose
REFMAC	refinement
HKL-2000	data reduction
HKL-2000	data scaling
MOLREP	phasing

Structure Validation

View Full Validation Report

Ligand Structure Quality Assessment

Entry History & Funding Information

Deposition Data

Released Date: 2021-11-17

Deposition Author(s):

Endo-Streeter, S.T.

Sondek, J.

Harden, T.K.

This entry supersedes: 3OHM

Funding Organization	Location	Grant Number
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)	United States	GM38213
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)	United States	GM57391
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)	United States	GM61454
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)	United States	GM074001
National Institutes of Health/National Eye Institute (NIH/NEI)	United States	EY010582