title: Structure of a delivery protein for an AAA+ protease in complex with a peptide degradation tag.
abstract: Substrate selection by AAA+ ATPases that function to unfold proteins or alter protein conformation is often regulated by delivery or adaptor proteins. SspB is a protein dimer that binds to the ssrA degradation tag and delivers proteins bearing this tag to ClpXP, an AAA+ protease, for degradation. Here, we describe the structure of the peptide binding domain of H. influenzae SspB in complex with an ssrA peptide at 1.6 A resolution. The ssrA peptides are bound in well-defined clefts located at the extreme ends of the SspB homodimer. SspB contacts residues within the N-terminal and central regions of the 11 residue ssrA tag but leaves the C-terminal residues exposed and positioned to dock with ClpX. This structure, taken together with biochemical analysis of SspB, suggests mechanisms by which proteins like SspB escort substrates to AAA+ ATPases and enhance the specificity and affinity of target recognition.
authors.affiliation: Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Igor
authors.initials: I
authors.lastname: Levchenko
authors.forename: Robert A
authors.initials: RA
authors.lastname: Grant
authors.forename: David A
authors.initials: DA
authors.lastname: Wah
authors.forename: Robert T
authors.initials: RT
authors.lastname: Sauer
authors.forename: Tania A
authors.initials: TA
authors.lastname: Baker
mesh_terms: D000251:Adenosine Triphosphatases / Q000737:chemistry* / Q000378:metabolism; D018360:Crystallography, X-Ray; D019281:Dimerization; D049071:Endopeptidase Clp; D006193:Haemophilus influenzae / Q000201:enzymology; D008954:Models, Biological; D008958:Models, Molecular; D005810:Multigene Family; D010455:Peptides / Q000737:chemistry*; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012329:RNA, Bacterial / Q000737:chemistry; D012697:Serine Endopeptidases / Q000737:chemistry*
chemical_list: D010455:Peptides; D012329:RNA, Bacterial; C096222:tmRNA; D012697:Serine Endopeptidases; D049071:Endopeptidase Clp; D000251:Adenosine Triphosphatases