3V42

Crystal structure of renal tumor suppressor protein, folliculin

Summary for 3V42

• Entry DOI: 10.2210/pdb3v42/pdb
• Descriptor: Folliculin (2 entities in total)
• Functional Keywords: folliculin, tumor suppressor, protein binding
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: Q8NFG4
• Total number of polymer chains: 2
• Total formula weight: 50933.22

Authors

Nookala, R.K.,Chirgadze, D.Y.,Blundell, T.L. (deposition date: 2011-12-14, release date: 2012-08-15, Last modification date: 2024-04-03)

Primary citation

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.
Crystal structure of folliculin reveals a hidDENN function in genetically inherited renal cancer.
Open Biol, 2:120071-120071, 2012

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.

PubMed: 22977732
DOI: 10.1098/rsob.120071

Experimental method

X-RAY DIFFRACTION (2 Å)