KOPS - Das Institutionelle Repositorium der Universität Konstanz

Structural insight into the environment of the serine/threonine protein kinase domain of titin

Structural insight into the environment of the serine/threonine protein kinase domain of titin

Zitieren

Dateien zu dieser Ressource

Prüfsumme: MD5:03016a7c45ee2fb412f91ea11c1ff809

MÜLLER, Simone, 2006. Structural insight into the environment of the serine/threonine protein kinase domain of titin [Dissertation]. Konstanz: University of Konstanz

@phdthesis{Muller2006Struc-6785, title={Structural insight into the environment of the serine/threonine protein kinase domain of titin}, year={2006}, author={Müller, Simone}, address={Konstanz}, school={Universität Konstanz} }

deposit-license The giant muscle protein titin is the largest polypeptide known and constitutes,<br />in addition to actin and myosin, the third filament system in the striated muscle sarcomere. Titin spans half of the sarcomere and interacts with many proteins along all its range. Three regions of accumulated interaction and associated signalling are found in the Z-disc, the I-band and the M-line, respectively.<br /><br />Among about 300 predicted domains in titin, to date only one has been identified<br />to comprise a catalytic function, a serine/threonine kinase domain within<br />the M-line, referred to as titin kinase . The aim of this work was to unravel the structural, molecular context of titin kinase in terms of adjacent titin domains and downstream signalling domains.<br /><br />The tandem immunoglobulin domains A168-A169 are located amino-terminal<br />to titin kinase at the end of the A-band within titin in the sarcomere. The structure solved in this work implies that these two domains are tightly connected via a continuous β-strand by merging of the last β-strand of A168 with the first of A169. A bulge is formed between two strands in A169 at a position which is rather uncommon for an insertion in an immunoglobulin (Ig) domain. This<br />insertion is involved in the interaction of A168-A169 with muscle specific RING<br />protein MURF-1. In addition to A168-A169, the carboxy-terminal domain to<br />titin kinase, the Ig domain M1 was solved.<br /><br />The proteins NBR1 and p62 are substrates of titin kinase, and NBR1 links p62<br />to titin kinase. The interaction of NBR1 and p62 within the signalling pathway<br />was studied here. Both proteins interact via their N-terminal PB1 domain, a<br />recently identified interaction domain. The structure of NBR1 PB1 was solved<br />as a single domain and in complex with p62 PB1. The complex reveals two<br />patches of positive (p62 PB1) and negative (NBR1 PB1) charge. The affinity<br />of the complex is in the nanomolar range.<br /><br />This work extends our structural knowledge about titin immunoglobulin domains.<br />Furthermore, it contributes to the understanding of interaction among<br />domains of the titin kinase downstream signalling pathway. Thereby, it may<br />help to unravel the connection between signalling related to titin stretching and transcription control in the context of muscle degradation. Müller, Simone 2011-03-24T17:29:10Z application/pdf 2011-03-24T17:29:10Z deu Structural insight into the environment of the serine/threonine protein kinase domain of titin 2006 Müller, Simone

Dateiabrufe seit 01.10.2014 (Informationen über die Zugriffsstatistik)

Diss_Simone_Mueller.pdf 740

Das Dokument erscheint in:

KOPS Suche


Stöbern

Mein Benutzerkonto