3V42

Crystal structure of renal tumor suppressor protein, folliculin

PDB DOI: https://doi.org/10.2210/pdb3V42/pdb

Classification: PROTEIN BINDING
Organism(s): Homo sapiens
Expression System: Escherichia coli
Mutation(s): Yes

Deposited: 2011-12-14 Released: 2012-08-15
Deposition Author(s): Nookala, R.K., Chirgadze, D.Y., Blundell, T.L.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 2.00 Å
R-Value Free: 0.268
R-Value Work: 0.204
R-Value Observed: 0.207

wwPDB Validation 3D Report Full Report

This is version 1.3 of the entry. See complete history.

Literature

Crystal structure of folliculin reveals a hidDENN function in genetically inherited renal cancer.

Nookala, R.K., Langemeyer, L., Pacitto, A., Ochoa-Montano, B., Donaldson, J.C., Blaszczyk, B.K., Chirgadze, D.Y., Barr, F.A., Bazan, J.F., Blundell, T.L.

(2012) Open Biol 2: 120071-120071

PubMed: 22977732 Search on PubMedSearch on PubMed Central
DOI: https://doi.org/10.1098/rsob.120071
Primary Citation of Related Structures:
3V42

PubMed Abstract:
Mutations in the renal tumour suppressor protein, folliculin, lead to proliferative skin lesions, lung complications and renal cell carcinoma. Folliculin has been reported to interact with AMP-activated kinase, a key component of the mammalian target of rapamycin pathway. Most cancer-causing mutations lead to a carboxy-terminal truncation of folliculin, pointing to a functional importance of this domain in tumour suppression. We present here the crystal structure of folliculin carboxy-terminal domain and demonstrate that it is distantly related to differentially expressed in normal cells and neoplasia (DENN) domain proteins, a family of Rab guanine nucleotide exchange factors (GEFs). Using biochemical analysis, we show that folliculin has GEF activity, indicating that folliculin is probably a distantly related member of this class of Rab GEFs.

Organizational Affiliation

Department of Biochemistry , University of Cambridge, Sanger Building, 80 Tennis Court Road, Cambridge CB2 1GA, UK. rn229@cam.ac.uk

Macromolecule Content

Total Structure Weight: 50.93 kDa
Atom Count: 3,308
Modelled Residue Count: 395
Deposited Residue Count: 452
Unique protein chains: 1

Macromolecules

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
Folliculin	A, B	226	Homo sapiens	Mutation(s): 3 Gene Names: BHD, FLCN
UniProt & NIH Common Fund Data Resources
Find proteins for Q8NFG4 (Homo sapiens) Explore Q8NFG4 Go to UniProtKB: Q8NFG4
PHAROS: Q8NFG4 GTEx: ENSG00000154803
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	Q8NFG4
Sequence Annotations Expand
Reference Sequence

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 2.00 Å
R-Value Free: 0.268
R-Value Work: 0.204
R-Value Observed: 0.207
Space Group: C 2 2 2₁

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 86.05	α = 90
b = 99.951	β = 90
c = 107.584	γ = 90

Software Package:

Software Name	Purpose
DNA	data collection
PHENIX	model building
REFMAC	refinement
XDS	data reduction
SCALA	data scaling
PHENIX	phasing

Structure Validation

View Full Validation Report

Entry History

Deposition Data

Released Date: 2012-08-15

Deposition Author(s):

Chirgadze, D.Y.

Revision History (Full details and data files)

Version 1.0: 2012-08-15
Type: Initial release
Version 1.1: 2012-09-26
Changes: Database references
Version 1.2: 2024-02-28
Changes: Data collection, Database references
Version 1.3: 2024-04-03
Changes: Refinement description

RCSB PDB Core Operations are funded by the National Science Foundation (DBI-1832184), the US Department of Energy (DE-SC0019749), and the National Cancer Institute, National Institute of Allergy and Infectious Diseases, and National Institute of General Medical Sciences of the National Institutes of Health under grant R01GM133198.