9.B.1.1.3 The CAAX integral membrane zinc prenyl metaloprotease, CAAX PP or Ste24p of 453 aas and 7 TMSs, found in every kingdom of eukaryotes. It's 3-D structure has been solved (Goblirsch and Wiener 2020). It is a factor responsible for processing the yeast mating a-factor pheromone. In animals, Ste24 processes prelamin, a component of the nuclear lamina; mutations in the human ortholog of Ste24 diminish its activity, giving rise to genetic diseases of accelerated aging (progerias). Additionally, lipodystrophy, acquired from the standard highly active antiretroviral therapy (HAART) used to treat AIDS patients, likely results from off-target interactions of HIV (aspartyl) protease inhibitor drugs with Ste24. Ste24 possesses a novel "α-barrel" structure, consisting of a ring of seven transmembrane α-helices enclosing a large (> 12,000 Å3) interior volume that contains the active-site and substrate-binding region; this "membrane-interior reaction chamber" is unprecedented in integral membrane protein structures. Additionally, the surface of the membrane-interior reaction chamber possesses a strikingly large negative electrostatic surface potential. Ste24p may be a key factor in several endoplasmic reticulum (ER) processes, including the unfolded protein response, a cellular stress response of the ER, and removal of misfolded proteins from the translocon. Ste24p is thus a "translocon unclogger". Goblirsch and Wiener 2020
have reviewed the sturcture and functions of Ste24. STE24p cleaves farnesylated prelamin A, the precursor of the nuclear scaffold protein lamin A (Wood et al. 2020).
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Accession Number: | P47154 |
Protein Name: | CAAX prenyl protease 1 |
Length: | 453 |
Molecular Weight: | 52324.00 |
Species: | Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast) [559292] |
Number of TMSs: | 5 |
Location1 / Topology2 / Orientation3: |
Endoplasmic reticulum membrane1 / Multi-pass membrane protein2 |
Substrate |
dimethylallyl-UTP |
---|
1: MFDLKTILDH PNIPWKLIIS GFSIAQFSFE SYLTYRQYQK LSETKLPPVL EDEIDDETFH
61: KSRNYSRAKA KFSIFGDVYN LAQKLVFIKY DLFPKIWHMA VSLLNAVLPV RFHMVSTVAQ
121: SLCFLGLLSS LSTLVDLPLS YYSHFVLEEK FGFNKLTVQL WITDMIKSLT LAYAIGGPIL
181: YLFLKIFDKF PTDFLWYIMV FLFVVQILAM TIIPVFIMPM FNKFTPLEDG ELKKSIESLA
241: DRVGFPLDKI FVIDGSKRSS HSNAYFTGLP FTSKRIVLFD TLVNSNSTDE ITAVLAHEIG
301: HWQKNHIVNM VIFSQLHTFL IFSLFTSIYR NTSFYNTFGF FLEKSTGSFV DPVITKEFPI
361: IIGFMLFNDL LTPLECAMQF VMSLISRTHE YQADAYAKKL GYKQNLCRAL IDLQIKNLST
421: MNVDPLYSSY HYSHPTLAER LTALDYVSEK KKN