Lympho-epithelial Kazal-type-related inhibitor (LEKTI) also known as serine protease inhibitor Kazal-type 5 (SPINK5) is a
protein that in humans is encoded by the SPINK5gene.[5][6]
Structure and function
LEKTI is a large multidomain
serine proteaseinhibitor expressed in stratified epithelial tissue. It consists of 15 domains that are cleaved into smaller, functional fragments by the protease
furin. Only two of these domains (2 and 15) contain 6 evenly spaced
cysteines responsible for 3 intramolecular
disulfide bonds characteristic of
Kazal-type related inhibitors. The remaining domains contain 4 cysteines.[7] These disulfide bonds force the molecule into a rigid conformation that enables the protein to interact with a target protease via an extended
beta-sheet. All domains (excepting 1, 2 and 15) contain an
arginine at P1, indicating trypsin-like proteases are the likely targets.[7]
LEKTI may play a role in skin and hair morphogenesis and anti-inflammatory and/or antimicrobial protection of mucous epithelia.[6]
Gene
SPINK5 is a member of a gene family cluster located on
chromosome 5q32,[10] which encode inhibitors of serine proteases. This includes other epidermal proteins
SPINK6 and
LEKTI-2 (SPINK9). The SPINK5 gene is 61 kb in length and contains 33 exons.[7] Alternative processing of SPINK5 results in the formation of three different gene products, which have been identified in differentiated keratinocytes.[11]
Clinical significance
Mutations in the SPINK5 gene result in
Netherton syndrome, a disorder characterized by
ichthyosis and specific immune system defects.[6]
^Mitsudo K, Jayakumar A, Henderson Y, Frederick MJ, Kang Y, Wang M, El-Naggar AK, Clayman GL (April 2003). "Inhibition of serine proteinases plasmin, trypsin, subtilisin A, cathepsin G, and elastase by LEKTI: a kinetic analysis". Biochemistry. 42 (13): 3874–81.
doi:
10.1021/bi027029v.
PMID12667078.
Walley AJ, Chavanas S, Moffatt MF, et al. (2001). "Gene polymorphism in Netherton and common atopic disease". Nat. Genet. 29 (2): 175–8.
doi:
10.1038/ng728.
PMID11544479.
S2CID20292050.
Ahmed A, Kandola P, Ziada G, Parenteau N (2002). "Purification and partial amino acid sequence of proteins from human epidermal keratinocyte conditioned medium". J. Protein Chem. 20 (4): 273–8.
doi:
10.1023/A:1010902815953.
PMID11594460.
S2CID11877191.