The SecA protein is a cell membrane associated subunit of the eubacterial Sec or Type II secretory pathway, a system which is responsible for the secretion of proteins through the cell membrane. Within this system the SecA

ATPase ATPases (, Adenosine 5'-TriPhosphatase, adenylpyrophosphatase, ATP monophosphatase, triphosphatase, SV40 T-antigen, ATP hydrolase, complex V (mitochondrial electron transport), (Ca2+ + Mg2+)-ATPase, HCO3−-ATPase, adenosine triphosphatase) are ...

forms a translocase complex with the SecYEG channel, thereby driving the movement of the protein

substrate Substrate may refer to: Physical layers *Substrate (biology), the natural environment in which an organism lives, or the surface or medium on which an organism grows or is attached ** Substrate (locomotion), the surface over which an organism lo ...

across the membrane.

Structure

SecA is a complex protein whose structure consists of six characterized domains that can explain SecA's capabilities to bind substrates and to move them. The following five domains seem to be present in all SecA proteins that have been structurally analyzed so far.

DEAD motor domain

This amino acid domain is subdivided into the two nucleotide binding folds 1 and 2 (NBF1 and NBF2) where

ATP ATP may refer to: Companies and organizations * Association of Tennis Professionals, men's professional tennis governing body * American Technical Publishers, employee-owned publishing company * ', a Danish pension * Armenia Tree Project, non ...

is bound and hydrolyzed. The chemical energy from the phosphodiester bonds results in a conformational change which is transferred to other domains (especially the HWD and the PPXD domains) which consequently mechanically move the

preprotein A protein precursor, also called a pro-protein or pro-peptide, is an inactive protein (or peptide) that can be turned into an active form by post-translational modification, such as breaking off a piece of the molecule or adding on another molecule ...

across the membrane. However, these conformational changes are partly regulated by other protomer domains described below.

C-terminal linker domain

The capability to bind to the SecB chaperone during post-translational translocation, the ribosome (during both post-translational translocation and co-translational translocation ) and the

phospholipid Phospholipids, are a class of lipids whose molecule has a hydrophilic "head" containing a phosphate group and two hydrophobic "tails" derived from fatty acids, joined by an alcohol residue (usually a glycerol molecule). Marine phospholipids typ ...

bilayer is important for SecA functioning and is achieved by the C-terminal linker domain.

Helical wing domain (HWD)

Located at the C-terminal portion of the molecule, this domain is in contact with the HSD and PPXD domains. Likely it plays a role in transferring molecular conformational motion, which it receives from HSD and which originates from ATP hydrolysis in the DEAD motor domain, to the PPXD domain.

Peptide cross linking domain (PPXD)

Since SecA's essential function is the transport of

across the membrane the ability to actually bind

must be given. The PPXD domain fulfils this function upon substrate binding.

Helical scaffold domain (HSD)

This domain lies in the center of the SecA protomer and contacts via α-helical interactions all other subdomains. In addition it contains the intramolecular regulator of ATP hydrolysis 1 (IRA1) subdomain which seems to prevent unwanted ATP hydrolysis when SecA is not bound to SecYEG. Together with IRA1, a conserved salt bridge called Gate 1 might function to prevent unnecessary conformational change. Gate 1 seems to functionally connect the nucleotide (

) binding site of the DEAD motor domain with the PPXD domain which results in regulation of ATP hydrolysis only upon

binding. However, this coordinative behaviour has only been shown to occur when SecA is bound to SecYEG.

References

{{reflist Protein targeting Protein domains Protein families Transmembrane proteins Secretion