The Tim21 binding domain connects the preprotein translocases of both mitochondrial membranes.
Proteins destined for the mitochondrial matrix are imported by the translocase of the outer membrane--the TOM complex--and the presequence translocase of the inner membrane--the TIM23 complex. At present, there is no structural information on components of the presequence translocase. Tim21, a subunit of the presequence translocase consisting of a membrane anchor and a carboxy-terminal domain exposed to the intermembrane space, directly connects the TOM and TIM23 complexes by binding to the intermembrane space domain of the Tom22 receptor. We crystallized the binding domain of Tim21 of Saccharomyces cerevisiae and determined its structure at 1.6 A resolution. The Tim21 structure represents a new alpha/beta-mixed protein fold with two alpha-helices flanked by an extended eight-stranded beta-sheet. We also identified a core sequence of Tom22 that binds to Tim21. Furthermore, negatively charged amino-acid residues of Tom22 are important for binding to Tim21. Here we suggest a mechanism for the TOM-TIM interaction.
Albrecht
Reinhard
R
Max-Planck-Institut für Biochemie, Abteilung Membranbiochemie, Am Klopferspitz 18, D-82512 Martinsried, Germany.
Rehling
Peter
P
Chacinska
Agnieszka
A
Brix
Jan
J
Cadamuro
Sergio A
SA
Volkmer
Rudolf
R
Guiard
Bernard
B
Pfanner
Nikolaus
N
Zeth
Kornelius
K
D000595:Amino Acid Sequence; D001665:Binding Sites; D002352:Carrier Proteins / Q000378:metabolism*; D003460:Crystallization; D026901:Membrane Transport Proteins / Q000737:chemistry* / Q000378:metabolism; D033681:Mitochondrial Membrane Transport Proteins; D051336:Mitochondrial Membranes / Q000378:metabolism*; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D008956:Models, Chemical; D008969:Molecular Sequence Data; D011498:Protein Precursors / Q000378:metabolism*; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012097:Repressor Proteins / Q000737:chemistry*; D012441:Saccharomyces cerevisiae / Q000737:chemistry / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000378:metabolism; D013329:Structure-Activity Relationship
D002352:Carrier Proteins; D026901:Membrane Transport Proteins; D033681:Mitochondrial Membrane Transport Proteins; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D011498:Protein Precursors; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; C090857:TOM22 protein, S cerevisiae; C500397:Tim21 protein, S cerevisiae