9.B.1.1.1 The CAAX prenyl protease CAAX PP, ZMPSTE24 (FACE1, STE24). The 3-d structure (2.0 Å resolution) revealed a seven TMS α-helical barrel structure surrounding a large water-filled intramembrane chamber capped by a zinc metalloprotease domain with the catlytic site facing into the chamber. Mutations cause laminopathies (Quigley et al. 2013). Results showed: (1) a detailed view of the active site of
ZMPSTE24, including water coordinating the catalytic zinc; (2) enhanced
visualization of fenestrations providing access from the exterior to the
interior cavity of the protein; (3) a view of the C-terminus extending
away from the main body of the protein; (4) localization of ordered
lipid and detergent molecules at internal and external surfaces and also
projecting through fenestrations, and (5) water molecules
associated with the surface of the internal cavity (Clark et al. 2017). A tripartite architecture of the human zinc metalloprotease Ste24 has been proposed (Goblirsch et al. 2019; see family description). ZMPSTE24 protects cells from SARS-CoV-2 spike-mediated pseudovirus infection and syncytia formation (Shilagardi et al. 2022).
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Accession Number: | O75844 |
Protein Name: | CAAX prenyl protease 1 homolog |
Length: | 475 |
Molecular Weight: | 54813.00 |
Species: | Homo sapiens (Human) [9606] |
Number of TMSs: | 7 |
Location1 / Topology2 / Orientation3: |
Endoplasmic reticulum membrane1 / Multi-pass membrane protein2 |
Substrate |
peptide, protein |
---|
1: MGMWASLDAL WEMPAEKRIF GAVLLFSWTV YLWETFLAQR QRRIYKTTTH VPPELGQIMD
61: SETFEKSRLY QLDKSTFSFW SGLYSETEGT LILLFGGIPY LWRLSGRFCG YAGFGPEYEI
121: TQSLVFLLLA TLFSALTGLP WSLYNTFVIE EKHGFNQQTL GFFMKDAIKK FVVTQCILLP
181: VSSLLLYIIK IGGDYFFIYA WLFTLVVSLV LVTIYADYIA PLFDKFTPLP EGKLKEEIEV
241: MAKSIDFPLT KVYVVEGSKR SSHSNAYFYG FFKNKRIVLF DTLLEEYSVL NKDIQEDSGM
301: EPRNEEEGNS EEIKAKVKNK KQGCKNEEVL AVLGHELGHW KLGHTVKNII ISQMNSFLCF
361: FLFAVLIGRK ELFAAFGFYD SQPTLIGLLI IFQFIFSPYN EVLSFCLTVL SRRFEFQADA
421: FAKKLGKAKD LYSALIKLNK DNLGFPVSDW LFSMWHYSHP PLLERLQALK TMKQH