{"doi":"10.1126/science.add5064","title":"Craspase is a CRISPR RNA-guided, RNA-activated protease","abstract":"The CRISPR-Cas type III-E RNA-targeting effector complex gRAMP/Cas7-11 is associated with a caspase-like protein (TPR-CHAT/Csx29) to form Craspase (CRISPR-guided caspase). Here, we use cryo-electron microscopy snapshots of Craspase to explain its target RNA cleavage and protease activation mechanisms. Target-guide pairing extending into the 5' region of the guide RNA displaces a gating loop in gRAMP, which triggers an extensive conformational relay that allosterically aligns the protease catalytic dyad and opens an amino acid side-chain-binding pocket. We further define Csx30 as the endogenous protein substrate that is site-specifically proteolyzed by RNA-activated Craspase. This protease activity is switched off by target RNA cleavage by gRAMP and is not activated by RNA targets containing a matching protospacer flanking sequence. We thus conclude that Craspase is a target RNA-activated protease with self-regulatory capacity.","journal":"Science","year":2022,"id":234627,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":94,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9616,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":850857,"name":"Sam P. B. van Beljouw","orcid":"0000-0003-3892-5028","position":1,"is_corresponding":false},{"id":850858,"name":"Ki Hyun Nam","orcid":"0000-0003-3268-354X","position":2,"is_corresponding":false},{"id":850692,"name":"Gabriel Schuler","orcid":"0000-0002-7666-5733","position":3,"is_corresponding":false},{"id":850859,"name":"Fran Ding","orcid":"0000-0001-6650-1236","position":4,"is_corresponding":false},{"id":850860,"name":"Yanru Cui","orcid":"0000-0002-2838-3491","position":5,"is_corresponding":false},{"id":850861,"name":"Alicia Rodríguez-Molina","orcid":"0000-0002-2368-0382","position":6,"is_corresponding":false},{"id":850862,"name":"Anna C. Haagsma","orcid":"0000-0001-7656-3932","position":7,"is_corresponding":false},{"id":850863,"name":"M. Valk","orcid":"0000-0002-3672-310X","position":8,"is_corresponding":false},{"id":850864,"name":"Martin Pabst","orcid":"0000-0001-9897-0723","position":9,"is_corresponding":false},{"id":641679,"name":"Stan J. J. Brouns","orcid":"0000-0002-9573-1724","position":10,"is_corresponding":false},{"id":646125,"name":"Ailong Ke","orcid":"0000-0001-5957-7822","position":11,"is_corresponding":false},{"id":850693,"name":"Chunyi Hu","orcid":"0000-0003-4509-4840","position":0,"is_corresponding":true}],"reference_count":36,"raw_metadata":null,"created_at":"2026-07-19T00:21:42.662304Z","pmid":"36007061","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}