BIP co-chaperone MTJ1/ERDJ1 interacts with inter-alpha-trypsin inhibitor heavy chain 4.
MTJ1/ERdj1 and its human homologue HTJ1 are membrane proteins that interact with the molecular chaperone BiP through their J-domain. HTJ1 also contains a C-terminal cytosolic region of unknown function that consists of two SANT domains separated by a spacer region. We recently showed that the second SANT domain of HTJ1 (SANT2) binds to alpha1-antichymotrypsin and alters its serpin activity [B. Kroczynska, C.M. Evangelista, S.S. Samant, E.C. Elguindi, S.Y. Blond, The SANT2 domain of the murine tumor cell DnaJ-like protein 1 human homologue interacts with alpha1-antichymotrypsin and kinetically interferes with its serpin inhibitory activity, J. Biol. Chem. 279 (2004) 11432-11443]. Here, we identified a new variant of human inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4) that also interacts with the SANT2 domain of HTJ1. Biochemical, mutagenesis, and fluorescence studies demonstrate that SANT2 binds to a carboxyl-terminal fragment that corresponds to the last third of the new ITIH4 isoform sequence (residues 588-930). ITIH4 and MTJ1 co-immunoprecipitate from total liver protein extracts and SANT2 protects the ITIH4(588-930) recombinant fragment from being processed by kallikrein in vitro. This work reveals that the SANT2 domain of HTJ1 is a genuine protein-protein interaction module.
Kroczynska
Barbara
B
Center for Pharmaceutical Biotechnology, University of Illinois at Chicago, Chicago, IL 60607, USA.
King-Simmons
LaShaunda
L
Alloza
Leonor
L
Alava
Maria A
MA
Elguindi
Ebrahim C
EC
Blond
Sylvie Y
SY
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001798:Blood Proteins / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D006023:Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D050956:HSP40 Heat-Shock Proteins; D006639:Histidine / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007610:Kallikreins / Q000378:metabolism; D008565:Membrane Proteins; D051379:Mice; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000235:genetics / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D017510:Protein Folding; D053491:Proteinase Inhibitory Proteins, Secretory; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014361:Trypsin Inhibitors / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D020798:Two-Hybrid System Techniques
D001798:Blood Proteins; C485368:DNAJC1 protein, human; D006023:Glycoproteins; D050956:HSP40 Heat-Shock Proteins; C471213:His-His-His-His-His-His; C091236:ITIH4 protein, human; D008565:Membrane Proteins; D018832:Molecular Chaperones; D009842:Oligopeptides; D010446:Peptide Fragments; D053491:Proteinase Inhibitory Proteins, Secretory; D011994:Recombinant Proteins; D014361:Trypsin Inhibitors; D006639:Histidine; D007610:Kallikreins