4l3t | pdb_00004l3t

Crystal Structure of Substrate-free Human Presequence Protease

spinqualitylabelsall models 4l3t, resolution 2.03Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4l3t is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: ACT, CAS, GOL, MLY, MLZ, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function PREP_HUMAN ATP-independent protease that degrades mitochondrial transit peptides after their cleavage. Also degrades other unstructured peptides. Specific for peptides in the range of 10 to 65 residues. Able to degrade amyloid beta A4 (APP) protein when it accumulates in mitochondrion, suggesting a link with Alzheimer disease. Shows a preference for cleavage after small polar residues and before basic residues, but without any positional preference. Publication Abstract from PubMed Human presequence protease (hPreP) is an M16 metalloprotease localized in mitochondria. There, hPreP facilitates proteostasis by utilizing an approximately 13,300-A3 catalytic chamber to degrade a diverse array of potentially toxic peptides, including mitochondrial presequences and beta-amyloid (Abeta), the latter of which contributes to Alzheimer disease pathogenesis. Here, we report crystal structures for hPreP alone and in complex with Abeta, which show that hPreP uses size exclusion and charge complementation for substrate recognition. These structures also reveal hPreP-specific features that permit a diverse array of peptides, with distinct distributions of charged and hydrophobic residues, to be specifically captured, cleaved, and have their amyloidogenic features destroyed. SAXS analysis demonstrates that hPreP in solution exists in dynamic equilibrium between closed and open states, with the former being preferred. Furthermore, Abeta binding induces the closed state and hPreP dimerization. Together, these data reveal the molecular basis for flexible yet specific substrate recognition and degradation by hPreP. Molecular Basis of Substrate Recognition and Degradation by Human Presequence Protease.,King JV, Liang WG, Scherpelz KP, Schilling AB, Meredith SC, Tang WJ Structure. 2014 Jun 11. pii: S0969-2126(14)00143-9. doi:, 10.1016/j.str.2014.05.003. PMID:24931469 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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