4DKK

The X-ray Crystal Structure of the Human STAU1 SSM-'RBD'5 Domain-Swapped Dimer

Summary for 4DKK

• Entry DOI: 10.2210/pdb4dkk/pdb
• Descriptor: Double-stranded RNA-binding protein Staufen homolog 1, CITRATE ANION, CHLORIDE ION, ... (4 entities in total)
• Functional Keywords: rbd, beta sheet, swapping-motif, dimerization, protein binding, rna binding protein
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: O95793
• Total number of polymer chains: 1
• Total formula weight: 12700.69

Authors

Gleghorn, M.L. (deposition date: 2012-02-03, release date: 2013-03-20, Last modification date: 2024-03-13)

Primary citation

Gleghorn, M.L.,Gong, C.,Kielkopf, C.L.,Maquat, L.E.
Staufen1 dimerizes through a conserved motif and a degenerate dsRNA-binding domain to promote mRNA decay.
Nat.Struct.Mol.Biol., 20:515-524, 2013

PubMed Abstract: Staufen1 (STAU1)-mediated mRNA decay (SMD) degrades mammalian-cell mRNAs that bind the double-stranded RNA (dsRNA)-binding protein STAU1 in their 3' untranslated region. We report a new motif, which typifies STAU homologs from all vertebrate classes, that is responsible for human STAU1 (hSTAU1) homodimerization. Our crystal structure and mutagenesis analyses reveal that this motif, which we named the Staufen-swapping motif (SSM), and the dsRNA-binding domain 5 ('RBD'5) mediate protein dimerization: the two SSM α-helices of one molecule interact primarily through a hydrophobic patch with the two 'RBD'5 α-helices of a second molecule. 'RBD'5 adopts the canonical α-β-β-β-α fold of a functional RBD, but it lacks residues and features required to bind duplex RNA. In cells, SSM-mediated hSTAU1 dimerization increases the efficiency of SMD by augmenting hSTAU1 binding to the ATP-dependent RNA helicase hUPF1. Dimerization regulates keratinocyte-mediated wound healing and many other cellular processes.

PubMed: 23524536
DOI: 10.1038/nsmb.2528

Experimental method

X-RAY DIFFRACTION (1.701 Å)