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Updated: Feb 19, 2026

Preparation of Mycobacterium Tuberculosis Culture Filtrate to Understand TB Pathogenesis
Published on: March 28, 2025
Mycobacterium tuberculosis Rv3651 is a triple sensor-domain protein
Jan Abendroth1,2, Andrew Frando3,4, Isabelle Q Phan2,3
1Beryllium Discovery, Bainbridge Island, Washington.
Abstract:
The genome of the human pathogen Mycobacterium tuberculosis (Mtb) encodes ∼4,400 proteins, but one third of them have unknown functions. We solved the crystal structure of Rv3651, a hypothetical protein with no discernible similarity to proteins with known function. Rv3651 has a three-domain architecture that combines one cGMP-specific phosphodiesterases, adenylyl cyclases and FhlA (GAF) domain and two Per-ARNT-Sim (PAS) domains. GAF and PAS domains are sensor domains that are typically linked to signaling effector molecules. Unlike these sensor-effector proteins, Rv3651 is an unusual sensor domain-only protein with highly divergent sequence. The structure suggests that Rv3651 integrates multiple different signals and serves as a scaffold to facilitate signal transfer.
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