Showing papers by "Raphael Guerois published in 2015"
TL;DR: Thermodynamic analysis of the quaternary complex together with structural modeling support that ASF1 andMCM2 could form a chaperoning module for histones H3 and H4 protecting them from promiscuous interactions suggests an additional function for MCM2 outside its helicase function as a proper histone chaperone connected to the replication pathway.
Abstract: MCM2 is a subunit of the replicative helicase machinery shown to interact with histones H3 and H4 during the replication process through its N-terminal domain. During replication, this interaction has been proposed to assist disassembly and assembly of nucleosomes on DNA. However, how this interaction participates in crosstalk with histone chaperones at the replication fork remains to be elucidated. Here, we solved the crystal structure of the ternary complex between the histone-binding domain of Mcm2 and the histones H3-H4 at 2.9 A resolution. Histones H3 and H4 assemble as a tetramer in the crystal structure, but MCM2 interacts only with a single molecule of H3-H4. The latter interaction exploits binding surfaces that contact either DNA or H2B when H3-H4 dimers are incorporated in the nucleosome core particle. Upon binding of the ternary complex with the histone chaperone ASF1, the histone tetramer dissociates and both MCM2 and ASF1 interact simultaneously with the histones forming a 1:1:1:1 heteromeric complex. Thermodynamic analysis of the quaternary complex together with structural modeling support that ASF1 and MCM2 could form a chaperoning module for histones H3 and H4 protecting them from promiscuous interactions. This suggests an additional function for MCM2 outside its helicase function as a proper histone chaperone connected to the replication pathway.
99 citations
TL;DR: The results demonstrate that the structural change of Kif2C-ATP upon binding to microtubule ends is sufficient for tubulin release, whereas ATP hydrolysis is not required.
20 citations
TL;DR: Improved alignments were systematically generated among the top k suboptimal alignments, which indicates that an optimal alignment by HHsearch may contain small to large errors, leading to poor structure prediction if these errors are located in important structures.
Abstract: MOTIVATION The HHsearch algorithm, implementing a hidden Markov model (HMM)-HMM alignment method, has shown excellent alignment performance in the so-called twilight zone (target-template sequence identity with ∼20%). However, an optimal alignment by HHsearch may contain small to large errors, leading to poor structure prediction if these errors are located in important structural elements. RESULTS HHalign-Kbest server runs a full pipeline, from the generation of suboptimal HMM-HMM alignments to the evaluation of the best structural models. In the HHsearch framework, it implements a novel algorithm capable of generating k-best HMM-HMM suboptimal alignments rather than only the optimal one. For large proteins, a directed acyclic graph-based implementation reduces drastically the memory usage. Improved alignments were systematically generated among the top k suboptimal alignments. To recognize them, corresponding structural models were systematically generated and evaluated with Qmean score. The method was benchmarked over 420 targets from the SCOP30 database. In the range of HHsearch probability of 20-99%, average quality of the models (TM-score) raised by 4.1-16.3% and 8.0-21.0% considering the top 1 and top 10 best models, respectively. AVAILABILITY AND IMPLEMENTATION http://bioserv.rpbs.univ-paris-diderot.fr/services/HHalign-Kbest/ (source code and server). CONTACT guerois@cea.fr. SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online.
10 citations