XPA-RPA Interactions (literature search)

Summary     References     Sequence     Structure

 

Summary:

RPA residues

XPA binding site

Specific Reference

RPA34C

XPA (1-58)

Li (Oct ’95)

XPA (29-46)

Bochkareva (Oct ’00)

UNG2 (73-88)≡XPA (29-46)

Bochkareva (Oct ’00)

RAD52 (257-274)≡XPA (20-46)

Bochkareva (Oct ’00)

UNG1 (57-79)≡XPA (20-46)

Krokan (Mar ’97)

XPA (4-29)

Tanaka (Dec ’96)

RPA70

XPA (153-176)

Li (Oct.’95)

RPA70

XPA (102-129) Zn domain

Tanaka (Aug ’98)

RPA70 N/C

XPA (138-182)

Tanaka (Aug ’98)

RPA70-SSB1 (183-296)

XPA-MBD (98-219)

Lowry (Jul ’03)

RPA70

XPA-MBD

Bochkareva (Oct ’00)

 

References:

A. Information on specific interaction sites

 

1.   Li et al. – Interactions sites on XPA.

XPA (153 to 176) contains domain for interaction with RPA70. This domain consists of three motifs just downstream the zinc finger motif. First 58 amino acid residues of XPA bind to RPA34. (Top)

 

  1. Lee (Feb. 2003) et al. – RPA-XPA interaction with XPC and DNA.

RPA34 C-term is the XPA interaction domain. (Top)

 

  1. Tanaka (Dec. 1996) et al. – Interaction sites on XPA.

XPA (4-29) interacts with RPA34 and XPA (98-187) interacts with RPA70. Simply, N-term of XPA & C-term of XPA interacts with RPA34 & RPA70 respectively. (Top)

 

  1. Krokan et al. – RPA32 interaction sites with UNG1. (Refer 1DPU in PDB)

UNG1 gene is homologous to XPA. UNG1 has an N-terminal pre-sequence which contains a region of 23 amino acids very similar to RPA34 binding domain of XPA. It was found that binding of RPA34 to UNG1 was dependent on the pre-sequence. C-term of RPA34 from 136 to 271 is sufficient for binding to UNG1. Residues 57-79 in UNG1 and 20-46 in XPA interact with RPA34. (Top)

 

  1. Lee (Apr. 1998) et al. – C-terminal of RPA34 is an interaction domain.

C-term of RPA34 is the primary interaction domain for XPA. Interaction of RPA with XPA does not require phosphorylation of RPA and can occur in the absence of DNA. (Top)

 

  1. Tanaka (Aug. 1998) et al. – RPA70 binds to Zn containing domain of XPA. (Refer 1XPA)

RPA70 is more involved in binding to XPA than RPA34. Zinc containing domain of XPA (102-129) is a binding domain for RPA70. C-term of XPA consists of a sheet-helix-loop region (138-182) which could bind with the N or C-term regions of RPA70. [C-term of XPA contains a cleft contributed by well-conserved Lys141, Lys145, Lys151, Lys179, Lys207 & Arg207. This cleft and surrounding area interact with DNA]. (Top)

 

  1. Bochkareva et al. – UNG2, RAD52, and XPA bind similarly to RPA32C.

C-term of RPA32 interacts with N-term of XPA. XPA 29-46 is sufficient for binding to RPA32. Direct interaction between DNA binding domains of XPA and RPA70 is suggested. [Sequences UNG2 (73-88), XPA (29-46) & RAD52 (257-274) interact with RPA32 in similar fashion . This kind of sequence may bias peptides toward helical conformations and thereby facilitate their interaction with RPA32C. N-term of RPA32 is not required for formation of complex with UNG2. Lys78, Arg84, Arg73, Arg76 & Arg88 of UNG2 are involved. Presence of flexible N-term suggests that RPA32C is an independent module that does not contact adjacent regions of RPA.] (Top)

 

  1. Lowry et al. – RPA 70 interaction sites + Summary of research in this topic. (Refer 1JMC)

It is shown that the minimal fragment of XPA (XPA-MBD: 98-219) necessary for DNA binding has an interaction with SSB1 (183-296) from RPA70. Also, the XPA-MBD-binding interface overlaps the ssDNA-binding interface on the surface of SSB1. It is possible that the observed interaction between RPA70 and XPA-MBD is too weak to be physiologically relevant. However, the observation that ssDNA and XPA-MBD compete for an overlapping site in RPA70 is consistent. (Top)

 

B.   General interaction information

 

  1. Dixon et al. – RPA-XPA interaction upon RPA phosphorylation.
  2. Yang et al. – RPA interaction with XPA2 (dimer).
  3. Tanaka (Feb. 1995) et al. – XPA interaction with RPA-34.
  4. Lee (Sep. 1995) et al. – XPAC interaction with RPA.
  5. Thelen et al. – XPF interaction with RPA.
  6. He et al. – RPA interaction with XPA and XPG. (Online copy not available)
  7. Lee (May 2000) et al. – RPA mutants interaction with XPA-DNA complex. (Top)

 

C. Other papers covered:

 

1.      Wyman et al.

2.      Aboussekhra et al.

3.      Sancar et al.

4.      Tanaka (Mar. 1999) et al.

5.      Naegeli et al.

6.      Krauss (Aug. 1999) et al.

7.      Krauss (Mar 2001) et al.

8.      Wood et al.

9.      Lee (Aug 2001) et al.                                                                                       (Top)

 

Pending:

1.      Turchi – ELSEVIER.

2.      Shirakawa  - ELSEVIER.

 

D. XPA sequence

 

1. Source: NP_000371 – XPA on NCBI protein sequence database [gi: 4507937].

 

  1 MAAADGALPE AAALEQPAEL PASVRASIER KRQRALMLRQ ARLAARPYSA TAAAATGGMA

 61 NVKAAPKIID TGGGFILEEE EEEEQKIGKV VHQPGPVMEF DYVICEECGK EFMDSYLMNH

121 FDLPTCDNCR DADDKHKLIT KTEAKQEYLL KDCDLEKREP PLKFIVKKNP HHSQWGDMKL

181 YLKLQIVKRS LEVWGSQEAL EEAKEVRQEN REKMKQKKFD KKVKELRRAV RSSVWKRETI

241 VHQHEYGPEE NLEDDMYRKT CTMCGHELTY EKM

 

2. Source: NP_003353 – UNG1 on NCBI protein sequence database [gi: 6224979].

 

  1 MGVFCLGPWG LGRKLRTPGK GPLQLLSRLC GDHLQAIPAK KAPAGQEEPG TPPSSPLSAE

 61 QLDRIQRNKA AALLRLAARN VPVGFGESWK KHLSGEFGKP YFIKLMGFVA EERKHYTVYP

121 PPHQVFTWTQ MCDIKDVKVV ILGQDPYHGP NQAHGLCFSV QRPVPPPPSL ENIYKELSTD

181 IEDFVHPGHG DLSGWAKQGV LLLNAVLTVR AHQANSHKER GWEQFTDAVV SWLNQNSNGL

241 VFLLWGSYAQ KKGSAIDRKR HHVLQTAHPS PLSVYRGFFG CRHFSKTNEL LQKSGKKPID

301 WKEL

 

E. XPA Structure

 

1.      1D4U – XPA-MBD that interacts with RPA70.

2.      1DPU – RPA32C interacting with UNG2 (homologous to XPA).

3.      1XPA – RPA binding domain of XPA.                                                 (Top)    

 

XPA interacts with RPA32C domain (domain in RPA70 is not clear), whose tertiary structure has been determined.

Please click on the links below to view:

 

1.      RPA32C – Figure obtained through VMD. (or check 1DPU in PDB)

2.      RPA70(181-432) – Figure obtained through VMD. (or check 1FGU in PDB)