Sampling the membrane: function of rhomboid-family proteins.
Rhomboids constitute a conserved protein superfamily that specifically binds membrane proteins and directs them into various different cellular pathways ranging from regulated secretion to endoplasmic reticulum (ER)-associated degradation (ERAD). Rhomboid proteases are known to release protein domains from membranes by a cut in their membrane anchor, whereas an emerging new class of rhomboid-family proteins lacks key catalytic residues and is not proteolytically active. Recent work has shown that these rhomboid pseudoproteases, including iRhoms and derlins, bind membrane proteins to regulate their fate, but the underlying molecular mechanism is not known. This review summarizes recent advances in the molecular understanding of rhomboid-family proteins and discusses common principles in how they recognize and bind proteins in the plane of the membrane.
Zentrum für Molekulare Biologie der Universität Heidelberg (ZMBH), DKFZ-ZMBH Allianz, Im Neuenheimer Feld 282, 69120 Heidelberg, Germany. m.lemberg@zmbh.uni-heidelberg.de
Marius K
MK
Lemberg
D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000737:chemistry / Q000378:metabolism; D020134:Catalytic Domain; D060746:Endoplasmic Reticulum-Associated Degradation; D006801:Humans; D008051:Lipid Bilayers / Q000378:metabolism*; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D008566:Membranes / Q000378:metabolism*; D045726:Metalloproteases / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D010447:Peptide Hydrolases / Q000378:metabolism; D021381:Protein Transport; D012697:Serine Endopeptidases / Q000737:chemistry / Q000378:metabolism; D056811:Unfolded Protein Response
C487709:DERL1 protein, human; D008051:Lipid Bilayers; D008565:Membrane Proteins; D045726:Metalloproteases; D010447:Peptide Hydrolases; C466104:RHBDL3 protein, human; D012697:Serine Endopeptidases; D016282:Aspartic Acid Endopeptidases