Anne Houdusse - Academia.edu (original) (raw)

Papers by Anne Houdusse

First-in-class drug candidate (MPH-220) efficiently improves spastic gait disorders by selective inhibition of fast skeletal muscle myosin-2

Biophysical Journal

Philosophical transactions of the royal society of london. Series B. Biological Sciences

Earth-Science Reviews, Dec 1, 1973

Cell, 2020

Highlights d A key residue variation of fast skeletal myosin allows selective targeting d A ratio... more Highlights d A key residue variation of fast skeletal myosin allows selective targeting d A rationally designed inhibitor (MPH-220) specifically blocks skeletal muscle d The inhibitor-bound myosin atomic structure reveals mechanism of selectivity d MPH-220 improves gait disorders in spastic animal model after brain injury

Crystal structure of myosin X motor domain with 2IQ motifs in pre-powerstroke state

Crystal Structure Of Myosin V Motor Domain - Nucleotide-Free

Crystal Structure Of Myosin V Motor With Essential Light Chain + ADP-BeFx - Near Rigor

Etude cristallographique d'un anticorps anti-idiotope, e5. 2

Http Www Theses Fr, 1992

L'unite d'immunologie structurale de l'institut pasteur etudie la structure tridimens... more L'unite d'immunologie structurale de l'institut pasteur etudie la structure tridimensionnelle des anticorps et des complexes antigene-anticorps monoclonaux au moyen de techniques radio-cristallographiques. D1. 3 est un anticorps monoclonal anti-lysozyme de blanc d'uf de poule. L'anticorps e5. 2 reconnait un idiotope prive de d1. 3. L'obtention de sa structure au moyen de la radiocristallographie suivie de projets permettant de localiser l'idiotope au niveau moleculaire devrait preciser un des sites antigeniques de d1. 3. La comparaison structurale de ce site avec le paratope et avec un autre idiotope de ce meme anticorps (site reconnu par un autre anticorps anti-idiotope nomme r225) pourra alors etre envisagee. Le travail cristallographique realise comporte l'etude du site de reconnaissance de l'anticorps e5. 2 non complexe. Les cristaux de fab e5. 2 comportent deux molecules par unite asymetrique. La resolution de la structure a ete effectuee par remplacement moleculaire. Cette etape a fait intervenir une fonction de translation particuliere appelee fonction de translation phasee plus rarement utilisee que les autres fonctions de translation. Apres affinement de la structure a moyenne resolution, le facteur r est egal a 18. 7% alors que la stereochimie du modele est correcte. La structure du fab e5. 2 a notamment permis d'identifier une conformation tout a fait particuliere pour le cdr3 de la chaine lourde long de 13 residus. La conformation de cette boucle sera comparee a celle d'autres anticorps. Afin d'identifier directement le site idiotope de d1. 3, l'obtention d'une forme cristalline complexee entre les deux anticorps a ete envisagee a partir des fragments fv obtenus apres clonage et expression de ces proteines dans une bacterie escherichia coli. Les etapes d'induction et d'expression des proteines ainsi que la purification conjointe des deux fragments fv ont ete realisees avec succes. Les essais de cristallisation du fv libre et du complexe entre les fv d1. 3 et e5. 2 sont en cours

Acta Crystallographica Section A Foundations of Crystallography, 1992

Although the phased translation function was first described some time ago [Colman, Fehlhammer & ... more Although the phased translation function was first described some time ago [Colman, Fehlhammer & Bartels (1976). In Crystallographic Computing Techniques, edited by F. R. Ahmed, K. Huml & B. Sedhi~ek, pp. 248-258. Copenhagen: Munksgaard], it has been little used, especially in the application of molecular replacement to macromolocular structures. Nevertheless, the procedure is relatively easy to apply and deserves wider use. In this paper the versatility of the phased translation function in a number of different applications is examined and experience gained in obtaining optimal results in protein structure determination by this method is reported. Examples given show how it can be used to position an oriented fragment, to locate independent components with respect to a common crystallographic origin and to choose correctly between enantiomorphic space groups. Its performance is compared with other translation functions in common use.

KIF20A is a critical kinesin for cell division and a promising anti-cancer drug target. The mecha... more KIF20A is a critical kinesin for cell division and a promising anti-cancer drug target. The mechanisms underlying its cellular roles remain elusive. Interestingly, unusual coupling between the nucleotide- and microtubule-binding sites of this kinesin-6 has been reported but little is known about how its divergent sequence leads to atypical motility properties. We present here the first high-resolution structure of its motor domain that delineates the highly unusual structural features of this motor, including a long L6 insertion that integrates into the core of the motor domain and that drastically affects allostery and ATPase activity. Together with the high-resolution cryo-EM microtubule-bound KIF20A structure that reveal the microtubule-binding interface, we dissect the peculiarities of the KIF20A sequence that work to favor fast dissociation of ADP, particularly in contrast to other kinesins. Structural and functional insights from the KIF20A pre-power stroke conformation thus h...

« Une myosine à contre-sens / A myosin that moves backwards »

Oncogene, 2021

Membrane Type 1 Matrix Metalloprotease (MT1-MMP) contributes to the invasive progression of breas... more Membrane Type 1 Matrix Metalloprotease (MT1-MMP) contributes to the invasive progression of breast cancers by degrading extracellular matrix tissues. Nucleoside diphosphate kinase, NME1/NM23-H1, has been identified as a metastasis suppressor; however, its contribution to local invasion in breast cancer is not known. Here, we report that NME1 is up-regulated in ductal carcinoma in situ (DCIS) as compared to normal breast epithelial tissues. NME1 levels drop in microinvasive and invasive components of breast tumor cells relative to synchronous DCIS foci. We find a strong anti-correlation between NME1 and plasma membrane MT1-MMP levels in the invasive components of breast tumors, particularly in aggressive histological grade III and triple-negative breast cancers. Knockout of NME1 accelerates the invasive transition of breast tumors in the intraductal xenograft model. At the mechanistic level, we find that MT1-MMP, NME1 and dynamin-2, a GTPase known to require GTP production by NME1 fo...

Biophysical Journal, 2021

Two-pore domain K þ (K 2P) channel activity is controlled by various stimuli that have been thoug... more Two-pore domain K þ (K 2P) channel activity is controlled by various stimuli that have been thought to finally converge at the selectivity filter (SF) gate. However, recent crystallographic studies have identified lower gates in TASK-1 and TASK-2 K 2P channels but pharmacological means to open these gates are currently unknown. Here, we report that TALK-2 K 2P channels also possess a lower gate by utilizing scanning mutagenesis, pore blocker analysis, permeant ion effects, chemical modification and MD simulations. Moreover, we report small molecule drugs and cellular lipids including long chain fatty acid esters (LC-CoAs) that open the lower gates in homomeric TASK-1, TALK-2 and TASK-1/TALK-2 heteromeric K 2P channels. Intriguingly, one of these openers is the pulmonary arterial hypertension (PAH) antidote ONO-RS-082 acting on PAH disease-gen TASK-1. Our results suggest that ONO-RS-082 open the lower gates by binding to the pore cavity when the lower gates are open which bears major implications for future design of PAH drugs. Finally, our results suggest a classification in the K 2P channel family with channels that exclusively utilize the SF gate (e.g. TREK-1/-2 and TRAAK), channels that exclusively utilize the lower gate (e.g. TASK-1) and K 2P channels with two functional gates (e.g. TALK-2 and TASK-2) highlighting the unusual diversity in structural gating mechanisms within this K þ channel family.

Microtubule-bound MKLP2 motor domain in the with no nucleotide

Myosin VI motor domain in the Pre-Transition State

Plasmodium falciparum Myosin A, post-rigor and rigor-like states

2nd PSL Chemical Biology Symposium (2019): At the Crossroads of Chemistry and Biology

ChemBioChem, 2019

Chemical Biology is the science of designing chemical tools to dissect and manipulate biology at ... more Chemical Biology is the science of designing chemical tools to dissect and manipulate biology at different scales. It provides the fertile ground from which to address important problems of our society, such as human health and environment.

Nucleotide-Free Scallop Myosin S1-NEAR Rigor State

Myosin Digested by Papain

Strucure of RAB6(GTP)-R6IP1 complex