Sec61 , termed SecYEG in prokaryotes, is a membrane protein complex found in all domains of life. As the core component of the translocon , it transports proteins to the endoplasmic reticulum in eukaryotes and out of the cell in prokaryotes. It is a doughnut-shaped pore through the membrane with 3 different subunits (heterotrimeric), SecY (α), SecE (γ), and SecG (β). It has a region called the plug that blocks transport into or out of the ER. This plug is displaced when the hydrophobic region of a nascent polypeptide interacts with another region of Sec61 called the seam, allowing translocation of the polypeptide into the ER lumen.
12-406: Although SecY and SecE are conserved in all three domains of life, bacterial SecG is only weakly homologous with eukaryotic Sec61β. The eukaryotic Sec61β is however homologous to the archaeal "SecG", leading some authors to refer to the archaeal complex as SecYEβ instead of SecYEG. (All three components of the archaeal complex are closer to their eukaryotic homologues than to their bacterial ones, but
24-492: A signal-peptide across the inner membrane in Gram-negative bacteria occurs via the preprotein translocase pathway. Proteins are produced in the cytoplasm as precursors, and require a chaperone subunit to direct them to the translocase component within the membrane. From there, the mature proteins are either targeted to the outer membrane or remain as periplasmic proteins. The translocase protein subunits are encoded on
36-522: Is a protein encoded by the SEC61A1 gene in humans. The protein encoded by this gene belongs to the SecY/Sec61α family. It plays a crucial role in the insertion of secretory and membrane polypeptides into the endoplasmic reticulum . This protein is found to be tightly associated with membrane-bound ribosomes , either directly or through adaptor proteins . This gene encodes an alpha subunit of
48-592: Is also encoded in the chloroplast genome of some algae where it could be involved in a prokaryotic-like protein export system across the two membranes of the chloroplast endoplasmic reticulum (CER) which is present in chromophyte and cryptophyte algae. SEC61A1 ; SEC61A2 ; SEC61A1 29927 53421 ENSG00000058262 ENSMUSG00000030082 P61619 P61620 NM_013336 NM_001400328 NM_001400329 NM_016906 NP_037468 NP_058602 Protein transport protein Sec61 subunit alpha isoform 1
60-403: Is resolved at 3.84 Å by cryo-EM in 2020, together with the rest of the co-translational translocon including the ribosome. The archaeal translocon is less understood. It might use SecDF - YajC and YidC like bacteria, as homologs have been found. An ATPase is yet to be identified. Human proteins: Budding yeast have two such homologous complexes; the essential one is named Sec61, and
72-468: The bacterial chromosome. The translocase pathway comprises 7 proteins, including a chaperone protein ( SecB ), an ATPase ( SecA ), an integral membrane complex (SecY, SecE, and SecG), and two additional membrane proteins that promote the release of the mature peptide into the periplasm (SecD and SecF). The chaperone protein SecB is a highly acidic homotetrameric protein that exists as a "dimer of dimers" in
84-524: The bacterial cytoplasm. SecB maintains preproteins in an unfolded state after translation and targets these to the peripheral membrane protein ATPase SecA for secretion. Cytoplasmic regions 2 and 3, and TM domains 1, 2, 4, 5, 7, and 10 are well conserved: the conserved cytoplasmic regions are believed to interact with cytoplasmic secretion factors, while the TM domains may participate in protein export. SecY
96-414: The front (lateral gate). SecE is a single spanning membrane protein in most species. It sits at the back of SecY, wrapping around the two halves of SecY. Secβ (SecG) is not essential. Its sits on the side of SecY and makes only few contacts with it. In a side view, the channel has an hourglass shape, with a cytoplasmic funnel that is empty, and an extracellular funnel that is filled with a little helix, called
108-462: The lateral gate into the lipid phase and become membrane-spanning segments. The bacterial SecYEG channel interacts with the signal sequences of secretory proteins as well as SecA , an ATPase which drives translocation. SecY is an integral plasma membrane membrane protein of 419 to 492 amino acid residues that typically contains 10 transmembrane (TM), 6 cytoplasmic and 5 periplasmic regions. Eukaryotic translocon uses BiP. The structure of human Sec61
120-538: The non-essential one is called Ssh1. Like Sec61, Ssh1 does dock to the ribosome. SecY protein The SecY protein is the main transmembrane subunit of the bacterial Sec export pathway and of a protein-secreting ATPase complex, also known as a SecYEG translocon . Homologs of the SecYEG complex are found in eukaryotes and in archaea, where the subunit is known as Sec61α. Secretion of some proteins carrying
132-423: The old two-empire names have become convention.) Much of the knowledge on the structure of the SecY/Sec61α pore comes from an X-ray crystallography structure of its archaeal version. The large SecY subunit consists of two halves, trans-membrane segments 1-5 and trans-membrane segments 6-10. They are linked at the extracellular side by a loop between trans-membrane segments 5 and 6. SecY can open laterally at
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#1732790452327144-425: The plug. In the middle of the membrane is a construction, formed from a pore ring of four hydrophobic amino acids that project their side chains inwards. During protein translocation, the plug is moved out of the way, and a polypeptide chain is moved from the cytoplasmic funnel, through the pore ring, the extracellular funnel, into the extracellular space. Hydrophobic segments of membrane proteins exit sideways through
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