The structure of the extracellular region of human hepsin reveals a serine protease domain and a novel scavenger receptor cysteine-rich (SRCR) domain.
Hepsin is an integral membrane protein that may participate in cell growth and in maintaining proper cell morphology and is overexpressed in a number of primary tumors. We have determined the 1.75 A resolution structure of the extracellular component of human hepsin. This structure includes a 255-residue trypsin-like serine protease domain and a 109-residue region that forms a novel, poorly conserved, scavenger receptor cysteine-rich (SRCR) domain. The two domains are associated with each other through a single disulfide bond and an extensive network of noncovalent interactions. The structure suggests how the extracellular region of hepsin may be positioned with respect to the plasma membrane.
Somoza
John R
JR
Celera, Inc., 180 Kimball Road, South San Francisco, CA 94080, USA. john.somoza@celera.com
Ho
Joseph D
JD
Luong
Christine
C
Ghate
Manjiri
M
Sprengeler
Paul A
PA
Mortara
Kyle
K
Shrader
William D
WD
Sperandio
David
D
Chan
Hedy
H
McGrath
Mary E
ME
Katz
Bradley A
BA
D000595:Amino Acid Sequence; D002462:Cell Membrane / Q000737:chemistry; D005110:Extracellular Space / Q000737:chemistry*; D006801:Humans; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011971:Receptors, Immunologic / Q000737:chemistry*; D051116:Receptors, Scavenger; D016415:Sequence Alignment; D012697:Serine Endopeptidases / Q000737:chemistry*
D011971:Receptors, Immunologic; D051116:Receptors, Scavenger; D012697:Serine Endopeptidases; C055645:hepsin