Identification of widespread adenosine nucleotide binding in Mycobacterium tuberculosis.
Computational prediction of protein function is frequently error-prone and incomplete. In Mycobacterium tuberculosis (Mtb), ~25% of all genes have no predicted function and are annotated as hypothetical proteins, severely limiting our understanding of Mtb pathogenicity. Here, we utilize a high-throughput quantitative activity-based protein profiling (ABPP) platform to probe, annotate, and validate ATP-binding proteins in Mtb. We experimentally validate prior in silico predictions of >240 proteins and identify 72 hypothetical proteins as ATP binders. ATP interacts with proteins with diverse and unrelated sequences, providing an expanded view of adenosine nucleotide binding in Mtb. Several hypothetical ATP binders are essential or taxonomically limited, suggesting specialized functions in mycobacterial physiology and pathogenicity.
Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99352, USA.
Charles
C
Ansong
Corrie
C
Ortega
Samuel H
SH
Payne
Daniel H
DH
Haft
Lacie M
LM
Chauvignè-Hines
Michael P
MP
Lewis
Anja R
AR
Ollodart
Samuel O
SO
Purvine
Anil K
AK
Shukla
Suereta
S
Fortuin
Richard D
RD
Smith
Joshua N
JN
Adkins
Christoph
C
Grundner
Aaron T
AT
Wright
D000241:Adenosine / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism*; D003198:Computer Simulation; D006801:Humans; D008954:Models, Biological; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D040901:Proteomics; D014376:Tuberculosis / Q000382:microbiology*
D001426:Bacterial Proteins; D000255:Adenosine Triphosphate; D000241:Adenosine