The DNA helicase activity of the xeroderma pigmentosum D protein, a crucial subunit of TFIID, is only needed for its role in DNA repair, not for transcription.

Obligate intracellular Chlamydia trachomatis replicate in a membrane-bound vacuole called inclusion, which serves as a signaling interface with the host cell. Here, we show that the chlamydial deubiquitinating enzyme (Cdu) 1 localizes in the inclusion membrane and faces the cytosol with the active deubiquitinating enzyme domain. The structure of this domain revealed high similarity to mammalian deubiquitinases with a unique α-helix close to the substrate-binding pocket. We identified the apoptosis regulator Mcl-1 as a target that interacts with Cdu1 and is stabilized by deubiquitination at the chlamydial inclusion. A chlamydial transposon insertion mutant in the Cdu1-encoding gene exhibited increased Mcl-1 and inclusion ubiquitination and reduced Mcl-1 stabilization. Additionally, inactivation of Cdu1 led to increased sensitivity of C. trachomatis for IFNγ and impaired infection in mice. Thus, the chlamydial inclusion serves as an enriched site for a deubiquitinating activity exerting a function in selective stabilization of host proteins and protection from host defense.DOI: http://dx.doi.org/10.7554/eLife.21465.001

Highlights d USP28 forms an active dimer d USP25 adopts an auto-inhibited tetrameric state d Cancer-associated mutations lead to active USP25 d Neither substrate nor ubiquitin chains disrupt the USP25 tetramer

The XPD helicase is a central component of the general transcription factor TFIIH which plays major roles in transcription and nucleotide excision repair (NER). Here we present the highresolution crystal structure of the Arch domain of XPD with its interaction partner MAT1, a central component of the CDK activating kinase complex. The analysis of the interface led to the identification of amino acid residues that are crucial for the MAT1-XPD interaction. More importantly, mutagenesis of the Arch domain revealed that these residues are essential for the regulation of (i) NER activity by either impairing XPD helicase activity or the interaction of XPD with XPG; (ii) the phosphorylation of the RNA polymerase II and RNA synthesis. Our results reveal how MAT1 shields these functionally important residues thereby providing insights into how XPD is regulated by MAT1 and defining the Arch domain as a major mechanistic player within the XPD scaffold.

Large filament proteins in muscle sarcomeres comprise many immunoglobulin-like domains that provide a molecular platform for self-assembly and interactions with heterologous protein partners. We have unravelled the molecular basis for the head-totail interaction of the carboxyl terminus of titin and the aminoterminus of obscurin-like-1 by X-ray crystallography. The binary complex is formed by a parallel intermolecular b-sheet that presents a novel immunoglobulin-like domain-mediated assembly mechanism in muscle filament proteins. Complementary binding data show that the assembly is entropy-driven rather than dominated data by specific polar interactions. The assembly observed leads to a V-shaped zipper-like arrangement of the two filament proteins.