4UAQ

Crystal structure of the accessory translocation ATPase, SecA2, from Mycobacterium tuberculosis

Summary for 4UAQ

• Entry DOI: 10.2210/pdb4uaq/pdb
• Descriptor: Protein translocase subunit SecA 2 (2 entities in total)
• Functional Keywords: protein transport, dead/deah box helicase preprotein translocation atp binding seca preprotein cross-linking domain, structural genomics, psi-2, protein structure initiative, tb structural genomics consortium, tbsgc
• Biological source: Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
• Cellular location: Cell membrane ; Peripheral membrane protein ; Cytoplasmic side : P9WGP3
• Total number of polymer chains: 1
• Total formula weight: 86057.60

Authors

Swanson-Smith, S.,Ioerger, T.R.,Rigel, N.W.,Miller, B.K.,Braunstein, M.,Sacchettini, J.C.,TB Structural Genomics Consortium (TBSGC) (deposition date: 2014-08-11, release date: 2015-09-09, Last modification date: 2024-10-09)

Primary citation

Swanson, S.,Ioerger, T.R.,Rigel, N.W.,Miller, B.K.,Braunstein, M.,Sacchettini, J.C.
Structural Similarities and Differences between Two Functionally Distinct SecA Proteins, Mycobacterium tuberculosis SecA1 and SecA2.
J.Bacteriol., 198:720-730, 2015

PubMed Abstract: While SecA is the ATPase component of the major bacterial secretory (Sec) system, mycobacteria and some Gram-positive pathogens have a second paralog, SecA2. In bacteria with two SecA paralogs, each SecA is functionally distinct, and they cannot compensate for one another. Compared to SecA1, SecA2 exports a distinct and smaller set of substrates, some of which have roles in virulence. In the mycobacterial system, some SecA2-dependent substrates lack a signal peptide, while others contain a signal peptide but possess features in the mature protein that necessitate a role for SecA2 in their export. It is unclear how SecA2 functions in protein export, and one open question is whether SecA2 works with the canonical SecYEG channel to export proteins. In this study, we report the structure of Mycobacterium tuberculosis SecA2 (MtbSecA2), which is the first structure of any SecA2 protein. A high level of structural similarity is observed between SecA2 and SecA1. The major structural difference is the absence of the helical wing domain, which is likely to play a role in how MtbSecA2 recognizes its unique substrates. Importantly, structural features critical to the interaction between SecA1 and SecYEG are preserved in SecA2. Furthermore, suppressor mutations of a dominant-negative secA2 mutant map to the surface of SecA2 and help identify functional regions of SecA2 that may promote interactions with SecYEG or the translocating polypeptide substrate. These results support a model in which the mycobacterial SecA2 works with SecYEG.

PubMed: 26668263
DOI: 10.1128/JB.00696-15

Experimental method

X-RAY DIFFRACTION (2.8 Å)