Work

Crystal Structure of a Hedgehog Autoprocessing Domain: Homology between Hedgehog and Self-Splicing Proteins

Year: 1997

Type: article

Abstract: The approximately 25 kDa carboxy-terminal domain of Drosophila Hedgehog protein (Hh-C) possesses an autoprocessing activity that results in an intramolecular cleavage of full-length Hedgehog protein and covalent attachment of a cholesterol moiety to the newly generated amino-terminal fragment. We have identified a 17 kDa fragment of Hh-C (Hh-C17) active in the initiation of autoprocessing and report here its crystal structure. The Hh-C17 structure comprises two homologous subdomains that appear to have arisen from tandem duplication of a primordial gene. Residues in the Hh-C17 active site have been identified, and their role in Hedgehog autoprocessing probed by site-directed mutagenesis. Aspects of sequence, structure, and reaction mechanism are conserved between Hh-C17 and the self-splicing regions of inteins, permitting reconstruction of a plausible evolutionary history of Hh-C and the inteins.

Source: Cell

DOI: 10.1016/s0092-8674(01)80011-8

Authors: Traci M.Tanaka Hall, Jeffery A. Porter, Keith E. Young, Eugene V. Koonin, Philip A. Beachy, Daniel J. Leahy

Institutions: Johns Hopkins University, Johns Hopkins Medicine, Howard Hughes Medical Institute, National Institutes of Health, National Center for Biotechnology Information

Language: English

Topic: Hedgehog Signaling Pathway Studies

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: hybrid

Estimated APC paid: $11,400

OpenAlex ID: W1990210405

FWCI: 6.411

Cites: 50

Cited by: 275

Related to: 10