Secs and chaperones: crystal structure of SecB

Abstract

Sec proteins are essential for the transport of periplasmic and outer membrane proteins through the bacterial cytoplasmic membrane. SecB binds to the nascent protein, inhibiting improper folding and, owing to its affinity for SecA, brings it to the cytoplasmic membrane. SecA is a peripheral membrane protein that, along with SecE and SecY, translocates the preprotein across the cytoplasmic membrane. Therefore, SecB has two functions; to chaperone preproteins and to bind SecA. What are the structural features of SecB that enables it to perform both tasks?Now, Xu et al. 1xCrystal structure of the bacterial protein export chaperone SecB. Xu, Z et al. Nat. Struct. Biol. 2000; 12: 1172–1177Crossref | Scopus (80)See all References1 address this pertinent question, using X-ray crystallography to determine the three-dimensional structure of SecB from Haemophilus influenzae to a resolution of 2.5 A. A homotetramer in solution, each monomer of SecB can be divided into two halves, the first of which consists of a four-stranded β-sheet, with the first two strands on opposite sides of the sheet connected by a ‘crossover’ loop. The second half of the molecule includes two antiparallel α-helices. The β-sheet wraps around helix α1 forming the hydrophobic core of the molecule. α1 is connected to the second helix through a long, hydrophobic, highly conserved loop, coined the ‘helix-connecting loop’. The second helix (α2) is free standing in solution after the third turn.Relating this structural information to function, the group predict which areas of the molecule are responsible for peptide binding and SecA binding. The peptide-binding site was predicted based on the fact that it must be on the surface of SecB, hydrophobic and flexible enough to bind a wide variety of proteins. Only one surface area of SecB – a groove formed between helix α2, strand β2, the crossover loop and the helix-connecting loop – meet these criteria. The SecA-binding site, predicted on the basis of mutagenesis studies along with charge and positioning considerations, is said to be on the solvent-exposed side of the β-sheet, resulting in a large acidic patch on the surface of the molecule.Xu et al. 1xCrystal structure of the bacterial protein export chaperone SecB. Xu, Z et al. Nat. Struct. Biol. 2000; 12: 1172–1177Crossref | Scopus (80)See all References1 discuss the fact that the tetrameric form of SecB is a clever piece of evolutionary engineering. Each subunit of the dimeric SecA can interact with one acidic region formed by each dimer of SecB. This could have a direct affect on the structure of the peptide-binding site, releasing the peptide, which then binds SecA. In this way, unlike the chaperones GroEL and DnaK, where the binding affinities for nascent proteins are regulated by the intrinsic ATPase activities, SecB is regulated by binding to SecA. This enables SecB to devote its entire molecular surface purely to its roles in the cell; chaperoning preproteins and delivering them to SecA.