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Article
| Open Access
Structural and functional dissection of the DH and PH domains of oncogenic Bcr-Abl tyrosine kinase
The Bcr-Abl tyrosine kinases p210 and p190 are linked to different leukemias and differ by the Dbl homology (DH) and Pleckstrin-homology (PH) domains. Here the authors characterize structures of the Bcr-Abl p210 DH and PH domains and find that the PH domain is important for the cellular localization and signaling network of p210.
- Sina Reckel
- , Charlotte Gehin
- & Oliver Hantschel
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Article
| Open Access
Structural basis for tRNA-dependent cysteine biosynthesis
tRNA-dependent cysteine biosynthesis is catalyzed by the transsulfursome protein complex. Here, the authors use a multidisciplinary approach to structurally characterize the archaeal transsulfursome and propose a model for tRNA channeling in the complex.
- Meirong Chen
- , Koji Kato
- & Min Yao
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Article
| Open Access
Structure and functional dynamics of the mitochondrial Fe/S cluster synthesis complex
Fe/S clusters are synthesized by the mitochondrial iron-sulfur cluster assembly (ISC) machinery. Here the authors combine crystallography and small angle X-ray scattering measurements to structurally characterize the core ISC complex and give functional insights into eukaryotic Fe/S cluster synthesis.
- Michal T. Boniecki
- , Sven A. Freibert
- & Miroslaw Cygler
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Article
| Open Access
A homologue of the Parkinson’s disease-associated protein LRRK2 undergoes a monomer-dimer transition during GTP turnover
The Parkinson’s disease‐associated LRRK2 protein is a multidomain Roco protein with GTPase activity. Here the authors use a multidisciplinary approach to characterize the GTPase mechanism of a homologous bacterial Roco protein and give mechanistic insights into disease-causing LRRK2 mutations.
- Egon Deyaert
- , Lina Wauters
- & Wim Versées
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Article
| Open Access
Three-dimensional context rather than NLS amino acid sequence determines importin α subtype specificity for RCC1
Importin α3 facilitates the nuclear transport of the Ran guanine nucleotide exchange factor RCC1. Here the authors reveal the molecular basis for the selectivity of RCC1 for importin α3 vs the generic importin α1 and discuss the evolution of importin α isoforms.
- Rajeshwer S. Sankhala
- , Ravi K. Lokareddy
- & Gino Cingolani
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Article
| Open Access
Molecular basis of human CD22 function and therapeutic targeting
The B-cell-specific co-receptor CD22 is a therapeutic target for depleting dysregulated B cells. Here the authors structurally characterize the ectodomain of CD22 and present its crystal structure with the bound therapeutic antibody epratuzumab, which gives insights into the mechanism of inhibition of B-cell activation.
- June Ereño-Orbea
- , Taylor Sicard
- & Jean-Philippe Julien
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Article
| Open Access
A shape-shifting redox foldase contributes to Proteus mirabilis copper resistance
Bacterial disulfide isomerases shuffle incorrect disulfide bonds. Here, the authors structurally characterize the disulfide isomerase ScsC fromProteus mirabilisand identify a functionally important shape-shifting motif that allows ScsC to adopt a diverse range of conformations and enable swarming in the presence of copper stress.
- Emily J. Furlong
- , Alvin W. Lo
- & Jennifer L. Martin
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Article
| Open Access
An elastic element in the protocadherin-15 tip link of the inner ear
Tip-link filaments convey force to activate hair cells, important sensory receptors. Here the authors solve a partial structure of human protocadherin-15, a tip-link component with an unusual Ca2+–free linker that bends and is predicted to confer flexibility to this filament during inner-ear mechanotransduction.
- Raul Araya-Secchi
- , Brandon L. Neel
- & Marcos Sotomayor
Dynamic intramolecular regulation of the histone chaperone nucleoplasmin controls histone binding and release