Rational correction of pathogenic conformational defects in HTRA1.

doi:10.1038/s41467-024-49982-8

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Article

Rational correction of pathogenic conformational defects in HTRA1.

Nature communications - 16 Jul 2024

Beaufort Nathalie, Ingendahl Linda, Merdanovic Melisa, Schmidt Andree, Podlesainski David, Richter Tim, Neumann Thorben, Kuszner Michael, Vetter Ingrid R, Stege Patricia, Burston Steven G, Filipovic Anto, Ruiz-Blanco Yasser B, Bravo-Rodriguez Kenny, Mieres-Perez Joel, Beuck Christine, Uebel Stephan, Zobawa Monika, Schillinger Jasmin, Malik Rainer, Todorov-Völgyi Katalin, Rey Juliana, Roberti Annabell, Hagemeier Birte, Wefers Benedikt, Müller Stephan A, Wurst Wolfgang, Sanchez-Garcia Elsa, Zimmermann Alexander, Hu Xiao-Yu, Clausen Tim, Huber Robert, Lichtenthaler Stefan F, Schmuck Carsten, Giese Michael, Kaiser Markus, Ehrmann Michael, Dichgans Martin

Abstract excerpt

Loss-of-function mutations in the homotrimeric serine protease HTRA1 cause cerebral vasculopathy. Here, we establish independent approaches to achieve the functional correction of trimer assembly defects. Focusing on the prototypical R274Q mutation, we identify an HTRA1 variant that promotes trimer formation thus restoring enzymatic activity in vitro. Genetic experiments in Htra1R274Q mice further demonstrate...

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Identifiers

PMID: 39013852
DOI: 10.1038/s41467-024-49982-8
PMCID: PMC11252331

Genes

HTRA1

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PubMed metadata and Literature Corpus relationships. Corpus snapshot updated 7 Sept 2026. Manifest publication-graph-cohort-2026-09-08.1.

Source receipt: pubmed, retrieved 7 Sept 2026.

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